Amiodarone - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

AMIODARONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N...

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AMIODARONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Amiodarone: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00055-5 1. Amiodarone-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on amiodarone. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON AMIODARONE ........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Amiodarone................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 11 The National Library of Medicine: PubMed ................................................................................ 12 CHAPTER 2. NUTRITION AND AMIODARONE ................................................................................. 59 Overview...................................................................................................................................... 59 Finding Nutrition Studies on Amiodarone.................................................................................. 59 Federal Resources on Nutrition ................................................................................................... 62 Additional Web Resources ........................................................................................................... 63 CHAPTER 3. ALTERNATIVE MEDICINE AND AMIODARONE........................................................... 65 Overview...................................................................................................................................... 65 National Center for Complementary and Alternative Medicine.................................................. 65 Additional Web Resources ........................................................................................................... 70 General References ....................................................................................................................... 71 CHAPTER 4. PATENTS ON AMIODARONE ....................................................................................... 73 Overview...................................................................................................................................... 73 Patents on Amiodarone................................................................................................................ 73 Patent Applications on Amiodarone ............................................................................................ 79 Keeping Current .......................................................................................................................... 82 CHAPTER 5. BOOKS ON AMIODARONE ........................................................................................... 83 Overview...................................................................................................................................... 83 Chapters on Amiodarone.............................................................................................................. 83 CHAPTER 6. PERIODICALS AND NEWS ON AMIODARONE ............................................................. 85 Overview...................................................................................................................................... 85 News Services and Press Releases................................................................................................ 85 Academic Periodicals covering Amiodarone ................................................................................ 88 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 89 Overview...................................................................................................................................... 89 U.S. Pharmacopeia....................................................................................................................... 89 Commercial Databases ................................................................................................................. 90 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 93 Overview...................................................................................................................................... 93 NIH Guidelines............................................................................................................................ 93 NIH Databases............................................................................................................................. 95 Other Commercial Databases....................................................................................................... 97 APPENDIX B. PATIENT RESOURCES ................................................................................................. 99 Overview...................................................................................................................................... 99 Patient Guideline Sources............................................................................................................ 99 Finding Associations.................................................................................................................. 101 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 103 Overview.................................................................................................................................... 103 Preparation................................................................................................................................. 103 Finding a Local Medical Library................................................................................................ 103 Medical Libraries in the U.S. and Canada ................................................................................. 103 ONLINE GLOSSARIES................................................................................................................ 109 Online Dictionary Directories ................................................................................................... 109

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AMIODARONE DICTIONARY ................................................................................................. 111 INDEX .............................................................................................................................................. 159

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with amiodarone is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about amiodarone, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to amiodarone, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on amiodarone. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to amiodarone, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on amiodarone. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON AMIODARONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on amiodarone.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and amiodarone, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “amiodarone” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Drug-Induced Liver Disease Source: Current Opinion in Gastroenterology. 12(3): 246-251. May 1996. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 700, Philadelphia, PA 19106. (215) 574-2266. Fax (215) 574-2292. Summary: This review article discusses recent developments with several important drug groups associated with drug-induced hepatotoxicity. The latest data indicate that nonsteroidal anti-inflammatory agents differ in the character, mechanism, incidence, and clinical importance of the hepatic injury that they may provoke. Reports of hepatotoxicity with flucloxacillin and amoxicillin-clavulanic acid continue despite publicity about risk factors. Concerns continue about adverse reactions to amiodarone, which should be prescribed only for serious cardiac arrhythmias. It is becoming quite

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clear that the threshold dose for hepatotoxicity from acetaminophen can be considerably lower than normal in regular users of alcohol. Evidence has also emerged that the mechanism of acetaminophen hepatotoxicity may involve release of cytotoxic mediators by hepatic macrophages in addition to the well-accepted mechanism of direct toxicity of an acetaminophen metabolite. The authors also discuss further developments in hepatotoxicity due to histamine H2-receptor antagonists, immunosuppressants, and steroid hormones. 2 tables. 58 references (19 annotated). (AA-M).

Federally Funded Research on Amiodarone The U.S. Government supports a variety of research studies relating to amiodarone. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to amiodarone. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore amiodarone. The following is typical of the type of information found when searching the CRISP database for amiodarone: •

Project Title: CONTROLLED RELEASE SYSTEMS FOR WATER-INSOLUBLE DRUGS Principal Investigator & Institution: Burke, Lagree M.; Polymer Science; University of Akron 302 Buchtel Mall Akron, Oh 44325 Timing: Fiscal Year 2002; Project Start 13-SEP-2002 Summary: The overall objectives of theis research are: (1) to increase to the apparent water solubilities and dissolution rates of water-insoluble drugs as to enhance their bioavailability, absorption and therapeutic efficacy by incorporating them in water-soluble polymers; (2) to investigate the interactions of drugs with the polymers and to develop an understanding of the dispersion morphologies; (3) to characterize the release of the drugs from the solid dispersions as a function of polymer molecular weight, drug loading and pH of the release medium; (4) to incorporate the solid dispersions in oral controlled-release (CR) systems that provide the delivery of the drugs at controlled rates over a specified time, where delivery is controlled by the device and not by the intrinsic water solubility of the drug; (5) to characterize the overall drug release rates with regard to the device parameters. The specific objectives of the proposed work are: (1) to incorporate griseofulvin (gris)/polyvinyl pyrrolidone (PVP) dispersions in matrix CR systems, (2) to characterize the overall drug release rates with regard to device parameters, and (3) to expand work in this area to include nifedipine, foscarnet, amiodarone and taxol.

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROLLED TRIAL FOR THE PREVENTION OF DEATH IN PATIENTS WITH CHF Principal Investigator & Institution: Hsia, Henry H.; Assistant Professor; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002 Summary: This study is a contribution of Temple Cardiology to a multi-institutional trial supported by NIH. The hypothesis tested is that amiodarone or an implantable cardioventer-defibrillator (ICD) will improve survival compared to placebo in patients with an LVEF less than, or equal to 35% and NYHA class II or III heart failure without VT or VF. Fifty patients will be accrued at Temple over 2.5 years with 2.5 year follow up in 50 institutions. The drug and placebo aims are blinded but not, of course, the ICD. The primary criterion is mortality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DATA COORDINATING CENTER FOR SCD IN HEART FAILURE TRIAL Principal Investigator & Institution: Lee, Kerry L.; Associate Professor of Biostatistics; Community and Family Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 30-APR-2003 Summary: The objective of this proposal is to establish the Statistical and Data Coordinating Center for the multicenter randomized clinical trial of prophylactic amiodarone or implantable defibrillator therapy vs. Conventional heart failure therapy in patients with Class II or Class III congestive heart failure (CHF) and an ejection fraction less than or equal to 35%. Qualifying patents (n=2,500) will be randomized in equal proportions to three treatments: conventional CHF therapy and placebo (control arm); conventional therapy combined with the use of amiodarone; and conventional therapy combined with a single lead, pectoral ICD that can be inserted on an outpatient basis. After discharge, all patients will be followed via clinic visits at 1 week, 4 weeks, 3 months, and every 3 months thereafter. Patients will be recruited over a period of 2.5 years, with a subsequent minimum follow-up of 2.5 years. The primary endpoint of the trial is all-cause mortality. Secondary endpoints include: 1) cardiac mortality and arrhythmic mortality; 2) ventricular tachycardia/fibrillation and bradyarrhythmias assessed via the ICD memory log; 3) morbidity; 4) quality of life; and 5) cost of care and cost effectiveness. In collaboration with the Clinical Coordinating Center (CCC) and the Economics and Quality of Life Center, the Data Coordinating Center will perform the following major functions: 1) participate in all phases of study planning; 2) coordinate the preparation of data collection forms; 3) prepare a manual of operations; 4) provide training/guidance in data collection procedures; 5) coordinate the randomization of patients; 6) organize the flow and management of all patient data; 7) establish high standards of quality control for data management; 8) perform on-site monitoring of completed data forms; 9) prepare regular status reports for the CCC and for all study committees; 10) dispense payments to clinical sites for enrolling and following patients; 11) perform appropriate statistical analyses of study data; and 12) participate in the preparation of study publications. Noteworthy features of this proposal include: a detailed assessment of sample size requirements; telephone randomization of patients; double data entry; on-site audits of data; economical and efficient computer hardware and software; state-of-the-art methods of data analysis; and an experienced team of

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investigators. Through the services it provides, the Data Coordinating Center will be a vital resource in the execution of this clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOPAMINE HOMEOSTASIS, VESICLES & NEURODEGENERATION Principal Investigator & Institution: Sonsalla, Patricia K.; Professor of Neurology; Neurology; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 088545635 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract) Parkinson's disease is a debilitating motor impairment disorder due to loss of nigral dopamine neurons. Mitochondrial defects in PD patients implicate energy impairment and metabolic stress as potential factors in its etiology. Moreover, DA oxidation products may add to the oxidative burden within DA neurons which, coupled with a persistent metabolic stress, may lead to neurodegeneration. Epidemiological studies link PD with environmental exposure to substances such as pesticides. - Many pesticides are mitochondrial inhibitors. A potential form of protection against mitochondrial toxins (i.e., MPP+) may be their sequestration into synaptic vesicles of DA neurons. The goal of this project is to gain an understanding of the role of vesicles, the vesicular monoamine transporter (VMAT2) and DA in modulating neurodegeneration produced by mitochondrial toxins. One hypothesis is that the actions of mitochondrial toxins can be modulated in contrasting ways depending on whether the toxins are sequestered into vesicles. If sequestered, toxin exposure could be abrogated. In contrast, disruption of vesicular function toxin could lead to disturbed DA homeostasis and enhanced toxicity since it would remove the toxin from interaction with mitochondria. In Aim 1 several mitochondrial toxins will be examined for their ability to interfere with vesicle function (i.e. to inhibit DA uptake into isolated rat membrane vesicles). In aim 2, rat mesencephalic cultures or rat striata will be exposed to mitochondrial toxins following VMAT2 inhibition to determine if toxicity is modified. To examine the hypothesis that disturbed DA homeostasis contributes to degeneration produced by metabolic stress, two approaches will be used. First, DA will be depleted prior to exposure of culture or rat striata to a mitochondrial inhibitor. Second, vesicle contents (DA) will be released into the cytosol after exposure to the mitochondrial toxin to examine if augmented disruption of DA homeostasis during the metabolic stress enhances toxicity. Additionally, the hypothesis that substances that are not themselves mitochondrial inhibitors, but can disrupt DA storage in vesicles may amplify damage during episodes of metabolic stress will be examined in Aim 3. In aim 4 the hypothesis that early events such as oxidative stress leads to loss of vesicle function, disruption of DA homeostasis and exacerbation of neurodegeneration produced by toxins will be investigated. Isolated vesicles will be tested for their sensitivity to oxidizing and reducing conditions. Results from these studies will provide novel and relevant information as to the contribution of VMAT2 containing vesicles in neuroprotection as well as in neurodegeneration of DA neurons during metabolic stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ECONOMICS AND QUALITY OF LIFE IN SCD HEFT Principal Investigator & Institution: Mark, Daniel B.; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 30-APR-2003

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Summary: The objective of this proposal is to establish an Economics and Quality of life Coordinating Center for SCD-HeFT, a multi-center clinical trial of prophylactic amiodarone or implantable defibrillator therapy versus conventional heart failure therapy in 2500 patients with Class II or Class III congestive heart failure (CHF) and an ejection fraction less than or equal to 35%. All patients will receive conventional CHF therapy. Qualifying patients will be randomized in equal proportions to either amiodarone placebo, active amiodarone therapy, or a single lead, pectoral ICD that can be inserted on an outpatient basis. Patients will be recruited into the trial over a period of 2.5 years, with a subsequent minimum follow-up period of 2.5 years. The primary endpoint of the trial is all-caused mortality. Cost, cost effectiveness, and health-related quality of life are secondary endpoints. In collaboration with the Clinical Coordinating Center and the Statistical and Data Coordinating Center, the Economics and Quality of Life Coordinating Center will perform the Following major function: (1) obtain baseline economics status and quality of life data from all patients enrolled at each participating study site at the time of randomization; (2) collect detailed health care resource consumption data for the index medical encounter; (3) assess economic, functional status, and quality of life outcomes during follow-up clinic visits at 3 months, 1 year, and 2.5 years after enrollment; (4) identify all medical encounters that occur during follow-up and collect detailed health care resource consumption and cost data for each; (5) compare cost and quality of life outcomes for the three treatment arms according to intention-to- treat; (6) estimate incremental cost effectiveness ratios for experimental arms and perform extensive sensitivity analyses. SCD-HeFT proposes a bold new approach to sudden death prevention as a primary prevention problem. However, the intervention strategies being tested have the potential for both significant beneficial and significant adverse clinical and quality of life effects. In addition, both involve increased health care costs. If efficacy is demonstrated for the primary clinical endpoint (all-cause mortality), then these economics and quality of life data will clearly be pivotal in determining how the results of this study are viewed and whether the superior therapeutic strategy (or strategies) receive widespread implementation. We propose to use stat-of-the-art methods for measuring cost and quality of life and for estimating cost effectiveness. This is a revised submission of HL55496-01. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF SUDDEN CARDIAC DEATH IN HEART FAILURE Principal Investigator & Institution: Murray, David; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2002 Summary: This is an NHLBI multi-center study to determine the effectiveness of amiodarone vs. implantable defibrillators (ICD) in preventing sudden cardiac death in patients with NYHA Class II-III congestive heart failure and ejection fractions of <35%. Patients will be randomized into three study arms: conventional treatment, conventional treatment plus amiodarone, and conventional treatment plus ICD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PSYCHOSOCIAL FACTORS IN SUDDEN CARDIAC DEATH Principal Investigator & Institution: Thomas, Sue A.; None; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005

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Summary: This proposal "Psychosocial Factor Outcome Study in Sudden Cardiac Death (PFOS)" constitutes an independent project complimentary to the ongoing NIH clinical trial, "Sudden Cardiac Death Heart Failure Trial (SCD-HeFT)." The PFOS study will 1) assess psychosocial (Psychological: anxiety, depression; social: social support, pet ownership, life stress) status of 300 patients enrolled in the SCD-HeFT clinical trial at baseline, after one month, and every six months for 2 years; 2) investigate the independent contributions of baseline psychosocial factors to survival of heart patients (HF) patients; 3) evaluate the impact of implanted cardioverter defibrillators (ICD) on the psychosocial status of heart failure (HF) patients who receive ICD as primary prevention for sudden cardiac death (SCD); and 4) compare the psychosocial impact of ICD with the impact of the other HF treatments. The SCD-HeFT, primary prevention trial, is designed to compare the effectiveness of three randomly assigned treatments in improving survival for patients with HF. The three treatments are: conventional therapy of HF and placebo, conventional therapy of HF and Amiodarone, and conventional therapy of HF and ICD. PFOS will utilize SCD-HeFT physiological and demographic data. Specific hypotheses will be tested with a minimum power of.8, using logistic multiple regression, linear multiple regression, chi-square, and multivariate analysis of variance. Heart failure affects 1-2 million people in the United States. As mortality from myocardial infarction has decreased due to improved treatment, the number of people living with HF has increased. Over half of the deaths from HF are due to SCD. The results of the PFOS have potential to influence nursing practice, save lives of HF patients, and prevent escalated health care costs as HF progresses. Nursing plays a major therapeutic role in the management of cardiac patients and their families. It is imperative to target interventions to maximize effectiveness at decreasing mortality and morbidity. The PFOS will identify a high-risk profile for HF patients. Using this profile, nurses can identify patients at greatest risk and develop interventions to modify the forms of psychosocial distress, which specifically contribute to SCD and long term psychosocial distress. The combination of data from PFOS and SCD-HeFT will provide a holistic assessment of HF patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RANDOMIZED CLINICAL TRIALS FOR PEDIATRIC HEART DISEASE Principal Investigator & Institution: Saul, J P.; Pediatrics; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by the applicant) The Children?s Heart Program of South Carolina is a statewide consortium of pediatric cardiologists, who care for 90% of the 3.7 million residents in the state. This consortium has all the critical elements for a center in the proposed research network: adequate patient volume, clinical research infrastructure, a track record of subject enrollment, and a demonstrated dedication to hypothesis driven clinical research. The applicant center, MUSC, is the tertiary referral center for the Children?s Heart Program. Current MUSC faculty have participated as PI?s in a total of 20 multicenter clinical trials or registries (10 open, 2 under IRB review). The PI of this application has been the lead investigator nationally in 4 of the 20. These protocols range from industry sponsored drug or device trials, to an NIH sponsored drug trial for fetal heart block, to an NIH prospective registry. The faculty also currently runs 11 local clinical research protocols. Participation in all of these protocols is supported by a dedicated pediatric cardiac research support group with 2 full time RN coordinators and an additional RN FTE. The combined resources of high volume and strong research

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infrastructure have enabled the PI?s at MUSC to be one of the top 2 subject recruiters in 6 of the 18 completed or active multicenter studies. As requested, the proposal contains a short-term and a long-term protocol. Short-Term. Randomized Trial of Aortopulmonary Collateral Coil Occlusion Prior to Fontan. Multiple factors influence morbidity and mortality for single ventricle patients undergoing Fontan operation. One considered recently is the presence of APC?s. However, multiple retrospective studies have failed to clearly delineate the role of APC?s or their optimum management. This protocol will prospectively evaluate the role of APC?s in postoperative Fontan hemodynamics and morbidity, and determine the importance of preoperative coil embolization in their management. Long-Term. Randomized Trial of Amiodarone vs Cooled- Tip Catheter Ablation for Treatment of Recurrent Intra-atrial Reentry Tachycardia (IART) in Patients with Congenital Heart Disease. IART, the single largest cause of morbidity late after repair of congenital heart disease, is often life-threatening, frustrating to treat and has no clearly superior therapy. This protocol will prospectively compare the most successful medical and catheter therapies for IART. The primary endpoint during a minimum of 2 years follow-up will be IART recurrence after successful ablation, or after drug loading and cardioversion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SCD HEFT: SUDDEN CARDIAC DEATH IN HEART FAILURE TRIAL Principal Investigator & Institution: Chinitz, Larry; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SUDDEN CARDIAC DEATH IN HEART FAILURE TRIAL Principal Investigator & Institution: Bardy, Gust H.; Seattle Institute for Cardiac Research Cardiac Research Seattle, Wa 98103 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 30-APR-2003 Summary: Congestive heart failure (CHF) is a common and lethal disease. A new diagnosis of CHF is made in 400,000 Americans each year. Those with moderate left ventricular dysfunction have a death rate of 25% over 2 1/2 years, with 50% thought to be due to arrhythmias. The central hypothesis of this study is that amiodarone or an implantable cardioverter-defibrillator (ICD) will improve survival compared to placebo in patients with NYHA Class II and Class III CHF and reduced left ventricular ejection fraction, less than or equal to 35%. The study will be a prospective, clinical trial with 2,500 patients randomly allocated in equal proportions to three different treatment arms over 2 1/2 years. The first arm of the study will consist of conventional heart failure therapy and placebo. The second arm of the study will combine conventional therapy with amiodarone. The third arm of the study will employ conventional therapy with a pectoral ICD. Treatment arms will be compared using an intention-to-treat analysis. We have one primary specific aim: 1. To compare all cause mortality-based on a minimum of 2 1/2 years of follow-up in the three arms of the study. We have five secondary specific aims: 1. To determine the incidence of cardiac mortality and arrhythmic mortality, 2. To determine the incidence of VT/VF and profound bradyarrhythmias (rates less than or equal to 30 bpm) in CHF patients in the ICD arm via the ICD memory log, 3. To compare morbidity in each of the three arms of the study, 4. To compare health-related quality of life in the three arms of the study, 5. To compare cost of care for

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each treatment group and calculate incremental cost-effectiveness ratios for the two intervention arms. The study will be performed at 95 North American Institutions. The Clinical Coordinating Center is the University of Washington in Seattle while the Data Coordinating Center and the Economics and Quality of Life Coordinating centers are at Duke University. The ICD Memory Log Core Laboratory is a subunit of the Clinical Coordinating Center focusing on secondary specific aim #2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUDDEN CARDIAC DEATH IN HEART FAILURE TRIAL OF PROPHYLACTIC AMIODARONE OR DEFIBRI Principal Investigator & Institution: Kaufman, Elizabeth S.; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002 Summary: Congestive heart failure is a common and lethal disease. Patients with moderate left ventricular dysfunction have a 25% mortality over 2.4 years. Fifty percent of these deaths are sudden and presumed arrhythmias in the majority of these sudden deaths. The hypothesis of this study is that Amiodarone or an implantable cardioverterdefibrilator will improve survival compared to placebo in patients with New York Heart Association Class II or III congestive heart failure and a left ventricular ejection fraction of less that or equal to 35%. This is a three arm study. Patients ramdomized to the first arm, "Conventional therapy", will receive standard CHF therapy including ACE inhibitors. The second arm, "Amiodarone vs. placebo", will be randomized to receive amiodarone vs. placebo. The third arm is, "implantable cardioverter-defibrillator (ICD)". Patients in this limb will receive a single lead device which will monitor for ventricular arrhythmias and will deliver a high voltage shock to return the rhythm to the normal one. This study may allow primary prevention of arrhythmic death in patients at high risk of this problem: patients with congestive heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRIGGERS OF VENTRICULAR ARRHYTHMIAS (TOVA) STUDY Principal Investigator & Institution: Muller, James E.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-1990; Project End 31-AUG-2004 Summary: This is an application for competitive renewal of our prior NHLBI grant that characterized triggering of non-fatal myocardial infarction (MI). We propose to apply the methods and findings of our MI study to characterize triggering of discharge of implantable cardioverter-defibrillators (ICDs). The long-term objective of the Triggers of Ventricular Arrhythmias (TOVA) Study is to gain insights into triggering useful for prevention of sudden cardiac death (SCD) due to primary arrhythmia in the general population; as a secondary objective we will obtain information useful for prevention of ICD discharge. Available evidence, largely anecdotal, indicates that activities associated with activation of the sympathetic nervous system trigger both SCD and ICD discharge. We will study patients with ICDs because 1) SCD victims cannot give historical triggering data, 2) ICD patients, who have a high rate of events, can be studied prospectively, and 3) electrograms from ICDs are a novel source for information about rate and rhythm prior to ICD discharge. TOVA study will utilize a cohort design with a nested case-crossover analysis, which permitted identification of triggering in over 17 percent of non-fatal MIs in our prior study. A pilot study of 164 patients with ICDs has demonstrated possible triggering in 23 percent of 39 discharges. We will characterize

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triggering in 2,000 episodes of ICD discharge in 3,000 patients treated in 44 centers nationwide over 4 years. Partial funding has been pledged by industry. The specific aims of this study are: 1) To identify activities, such as heavy exertion, that trigger ICD discharge; 2) To determine factors, such as beta-blockade, that modify the susceptibility to triggering; 3) To determine if ICD discharges occur more frequently in the 3 hours after awakening, on Monday, and in winter; and, 4) To utilize electrograms recorded prior to ICD discharge to identify sympathetic activation during triggering. Characterization of triggering of ICD discharge will provide insights valuable for prevention of sudden death due to primary arrhythmias in the general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “amiodarone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for amiodarone in the PubMed Central database: •

Action of Amiodarone over the Extension and Reversibility of Experimental Myocardial Infarction in Pigs. by Alvarez CB, Castelli A, Grassi E, Celener D, Rapapport M, Martin J.; 1984 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351709

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Antagonism of thyroid hormone action by amiodarone in rat pituitary tumor cells. by Norman MF, Lavin TN.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303675

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Asymptomatic Cavitary Pneumonitis Due to Amiodarone Pulmonary Toxicity. by Schechter CJ, O'Neill G, Schweppe HI Jr, Klima T, Treistman B.; 1985 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341893

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Electrophysiologic Testing: Predictive of Amiodarone Efficacy in Recurrent Sustained Ventricular Tachycardia? by Mas IJ, Massumi A, Harlan M, Seger JJ, Hall RJ.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324762

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Programmed electrical stimulation and Amiodarone therapy for the control of persistent junctional tachycardia. by Critelli G, Adinolfi L, Perticone F, Condorelli M.; 1981 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287922

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Use of amiodarone in the postmyocardial infarction patient. by Ozdil E, Carlson TA, Massumi A.; 1995; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325209

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with amiodarone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “amiodarone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for amiodarone (hyperlinks lead to article summaries): •

A randomized clinical trial of the efficacy of radiofrequency catheter ablation and amiodarone in the treatment of symptomatic atrial fibrillation. Author(s): Krittayaphong R, Raungrattanaamporn O, Bhuripanyo K, Sriratanasathavorn C, Pooranawattanakul S, Punlee K, Kangkagate C. Source: J Med Assoc Thai. 2003 May; 86 Suppl 1: S8-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12866763

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A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation. Author(s): Channer KS, Birchall A, Steeds RP, Walters SJ, Yeo WW, West JN, Muthusamy R, Rhoden WE, Saeed BT, Batin P, Brooksby WP, Wilson I, Grant S. Source: European Heart Journal. 2004 January; 25(2): 144-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720531

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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A simplified amiodarone regimen to prevent postoperative atrial fibrillation. Author(s): Drucker MH, Smith I. Source: The Annals of Thoracic Surgery. 2003 June; 75(6): 2008; Author Reply 2009. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12822666

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Acute amiodarone-induced pulmonary toxicity following lung resection. Author(s): Handschin AE, Lardinois D, Schneiter D, Bloch K, Weder W. Source: Respiration; International Review of Thoracic Diseases. 2003 May-June; 70(3): 310-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915754

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Acute circulatory actions of intravenous amiodarone loading in cardiac surgical patients. Author(s): Cheung AT, Weiss SJ, Savino JS, Levy WJ, Augoustides JG, Harrington A, Gardner TJ. Source: The Annals of Thoracic Surgery. 2003 August; 76(2): 535-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902100

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Acute electrophysiologic effects of intravenous amiodarone are independent of a sympatholytic action in humans. Author(s): Haikerwal D, Esler MD, Dart AM. Source: Journal of Cardiovascular Pharmacology. 2003 May; 41(5): 760-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12717107

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Acute hepatitis after parenteral amiodarone. Author(s): Olsson R. Source: Ital Heart J. 2003 May; 4(5): 355-6; Author Reply 356-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848097

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Acute pulmonary injury in association with amiodarone. Author(s): Brinker A, Johnston M. Source: Chest. 2004 April; 125(4): 1591-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078784

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Amiodarone and breast feeding. Author(s): Hall CM, McCormick KP. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 May; 88(3): F255-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12719404

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Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation. Author(s): Khan IA, Mehta NJ, Gowda RM. Source: International Journal of Cardiology. 2003 June; 89(2-3): 239-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767548

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Amiodarone for postoperative atrial fibrillation. Author(s): Yazigi A, Haddad F, Madi-Jebara S, Sleilaty G, Jebara VA. Source: The Journal of Thoracic and Cardiovascular Surgery. 2004 January; 127(1): 304; Author Reply 304-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752462

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Amiodarone induced thyrotoxicosis: diagnostic and therapeutic strategies. Author(s): Cardenas GA, Cabral JM, Leslie CA. Source: Cleve Clin J Med. 2003 July; 70(7): 624-6, 628-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882384

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Amiodarone reduces the incidence of atrial fibrillation after coronary artery bypass grafting. Author(s): Yagdi T, Nalbantgil S, Ayik F, Apaydin A, Islamoglu F, Posacioglu H, Calkavur T, Atay Y, Buket S. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 June; 125(6): 1420-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830063

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Amiodarone therapy before heart transplantation as a predictor of thyroid dysfunction after transplantation. Author(s): Siccama R, Balk AH, de Herder WW, van Domburg R, Vantrimpont P, van Gelder T. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 August; 22(8): 857-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909464

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Amiodarone therapy for drug-refractory fetal tachycardia. Author(s): Strasburger JF, Cuneo BF, Michon MM, Gotteiner NL, Deal BJ, McGregor SN, Oudijk MA, Meijboom EJ, Feinkind L, Hussey M, Parilla BV. Source: Circulation. 2004 January 27; 109(3): 375-9. Epub 2004 Jan 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732753

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Amiodarone versus implantable cardioverter-defibrillator:randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia--AMIOVIRT. Author(s): Strickberger SA, Hummel JD, Bartlett TG, Frumin HI, Schuger CD, Beau SL, Bitar C, Morady F; AMIOVIRT Investigators. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1707-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767651

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Amiodarone: guidelines for use and monitoring. Author(s): Siddoway LA. Source: American Family Physician. 2003 December 1; 68(11): 2189-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677664

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Amiodarone-induced 2 to 1 atrioventricular block in association with prolongation of the QT interval. Author(s): McMahon CJ, Laird WP, Fenrich AL. Source: Cardiology in the Young. 2003 June; 13(3): 305-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12903882

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Amiodarone-induced peri-oral photosensitivity. Author(s): Shah N, Warnakulasuriya S. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2004 January; 33(1): 56-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675142

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Amiodarone-induced systemic lupus erythematosus. Author(s): Kundu AK. Source: J Assoc Physicians India. 2003 February; 51: 216-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725272

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Basal cell carcinoma following amiodarone therapy. Author(s): Monk BE. Source: The British Journal of Dermatology. 1995 July; 133(1): 148-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7669632

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Beneficial effect of amiodarone on cardiac mortality in patients with asymptomatic complex ventricular arrhythmias after acute myocardial infarction and preserved but not impaired left ventricular function. Author(s): Pfisterer M, Kiowski W, Burckhardt D, Follath F, Burkart F. Source: The American Journal of Cardiology. 1992 June 1; 69(17): 1399-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1590226

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Beneficial effect of amiodarone on pacing induced terminability of reentrant ventricular tachycardia. Author(s): Chinushi M, Uchiyama H, Nakagawa I, Washizuka T, Aizawa Y. Source: Japanese Heart Journal. 1999 July; 40(4): 471-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10611912

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Beneficial effects of amiodarone in heart failure: interaction with beta-adrenoceptors rather than G proteins. Author(s): Schnabel P, Mies F, Maack C, Rosenkranz S, Zolk O, Bohm M. Source: European Journal of Pharmacology. 1999 March 26; 369(3): 391-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10225379

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Beta-blockade and amiodarone therapy: twin brothers from different parents. Author(s): Eichhorn EJ, Hamdan MH. Source: Journal of Cardiac Failure. 1998 December; 4(4): 289-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9924850

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Beta-blocker prevention of proarrhythmia and proischemia: clues from CAST, CAMIAT, and EMIAT. Cardiac Arrhythmia Suppression Trial. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial. European Myocardial Infarct Amiodarone Trial. Author(s): Kennedy HL. Source: The American Journal of Cardiology. 1997 November 1; 80(9): 1208-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9359552

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Beta-blockers and amiodarone for the primary prevention of sudden cardiac death. Author(s): Frankenberger O, Steinberg JS. Source: Current Cardiology Reports. 1999 November; 1(4): 274-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980854

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Bilateral anterior ischaemic optic neuropathy following amiodarone. Author(s): Palimar P, Cota N. Source: Eye (London, England). 1998; 12 ( Pt 5): 894-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10070533

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Bilateral atrial function after chemical cardioversion of atrial fibrillation with amiodarone: an echo-Doppler study. Author(s): Escudero EM, San Mauro M, Laugle C. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 1998 April; 11(4): 365-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9571586

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Bilateral optic neuropathy linked with amiodarone. Author(s): Seemongal-Dass RR, Spencer SR. Source: Eye (London, England). 1998; 12 ( Pt 3A): 474-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9775253

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Bioavailability of amiodarone tablets administered with and without food in healthy subjects. Author(s): Meng X, Mojaverian P, Doedee M, Lin E, Weinryb I, Chiang ST, Kowey PR. Source: The American Journal of Cardiology. 2001 February 15; 87(4): 432-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11179527

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Bleeding complication during coumarin therapy due to amiodarone and azithromycin. Author(s): Bharat V, Mohanty B. Source: J Assoc Physicians India. 2000 July; 48(7): 746-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11273517

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Bone marrow granulomas possibly associated with amiodarone. Author(s): Yamreudeewong W, McIntyre WW, Sun TJ, Ranelli PL. Source: Pharmacotherapy. 2000 July; 20(7): 855-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10907978

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Bradycardia-facilitated polymorphic ventricular tachycardia caused by amiodarone after radiofrequency modification of atrioventricular conduction. Author(s): Williamson BD, Hummel J, Niebauer M, Man KC, Strickberger SA, Daoud E, Morady F. Source: American Heart Journal. 1995 August; 130(2): 399-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7631627

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Bronchiolitis obliterans organising pneumonia secondary to amiodarone treatment. Author(s): Anton Aranda E, Alkiza Basanez R, Laplaza Jimenez Y. Source: The Netherlands Journal of Medicine. 1998 September; 53(3): 109-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9803141

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Bronchiolitis obliterans organizing pneumonia during low-dose amiodarone therapy. Author(s): Jessurun GA, Hoogenberg K, Crijns HJ. Source: Clin Cardiol. 1997 March; 20(3): 300-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9068921

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Bronchiolitis obliterans organizing pneumonia secondary to amiodarone: a rare aetiology. Author(s): Valle JM, Alvarez D, Antunez J, Valdes L. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1995 March; 8(3): 470-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7789497

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Bronchiolitis obliterans organizing pneumonia secondary to amiodarone: clinical, radiological and histological pattern. Author(s): Conte SC, Pagan V, Murer B. Source: Monaldi Arch Chest Dis. 1997 February; 52(1): 24-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151516

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Bronchoalveolar lavage cell count and differential are not reliable indicators of amiodarone-induced pneumonitis. Author(s): Ohar JA, Jackson F, Dettenmeier PA, Bedrossian CW, Tricomi SM, Evans RG. Source: Chest. 1992 October; 102(4): 999-1004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1395816

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Bronchoalveolar lavage cell data in amiodarone-associated pneumonitis. Evaluation in 22 patients. Author(s): Akoun GM, Cadranel JL, Blanchette G, Milleron BJ, Mayaud CM. Source: Chest. 1991 May; 99(5): 1177-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1673380

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Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone. Author(s): Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O'Brien B. Source: Circulation. 2000 March 21; 101(11): 1297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10725290

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Clinical experience of amiodarone-induced thyrotoxicosis over a 3-year period: role of colour-flow Doppler sonography. Author(s): Eaton SE, Euinton HA, Newman CM, Weetman AP, Bennet WM. Source: Clinical Endocrinology. 2002 January; 56(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11849244

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Clinical observations with the amiodarone/warfarin interaction: dosing relationships with long-term therapy. Author(s): Sanoski CA, Bauman JL. Source: Chest. 2002 January; 121(1): 19-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11796427

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Clinical picture: Amiodarone-induced pulmonary mass and cutaneous vasculitis. Author(s): Scharf C, Oechslin EN, Salomon F, Kiowski W. Source: Lancet. 2001 December 15; 358(9298): 2045. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755612

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Clinical picture: amiodarone-induced thyroiditis. Author(s): Ybarra J, Fuster D, Martin F, Lomena F, Torregrossa JV. Source: Lancet. 2002 January 5; 359(9300): 69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11809205

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Clinical usefulness of electrophysiologic testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy treated with amiodarone or sotalol. Author(s): Leite LR, Fenelon G, Simoes A Jr, Silva GG, Friedman PA, de Paola AA. Source: Journal of Cardiovascular Electrophysiology. 2003 June; 14(6): 567-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875414

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Clusters of ventricular fibrillation in a patient with an implantable cardioverter difibrillator treated with amiodarone. Author(s): Emori T, Ohta K, Kusano K, Morita H, Matsubara H, Sano S, Ohe T. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 February; 67(2): 163-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548001

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Coital headaches induced by amiodarone. Author(s): Biran I, Steiner I. Source: Neurology. 2002 February 12; 58(3): 501-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11839867

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Combination therapy with carvedilol and amiodarone in patients with severe heart failure. Author(s): Nagele H, Bohlmann M, Eck U, Petersen B, Rodiger W. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2000 March; 2(1): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10742706

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Comparison of amiodarone versus ibutilide for the prevention of immediate recurrences of atrial fibrillation during pulmonary vein isolation. Author(s): Oral H, Ozaydin M, Tada H, Chugh A, Hassan S, Scharf C, Lai SW, Greenstein R, Pelosi F Jr, Knight BP, Strickberger SA, Morady F. Source: The American Journal of Cardiology. 2002 September 1; 90(5): 492-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208408

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Comparison of digoxin versus low-dose amiodarone for ventricular rate control in patients with chronic atrial fibrillation. Author(s): Tse HF, Lam YM, Lau CP, Cheung BM, Kumana CR. Source: Clinical and Experimental Pharmacology & Physiology. 2001 May-June; 28(5-6): 446-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11380520

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Comparison of plasma concentrations for two amiodarone products. Author(s): Sauro SC, DeCarolis DD, Pierpont GL, Gornick CC. Source: The Annals of Pharmacotherapy. 2002 November; 36(11): 1682-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398559

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Comparison of survival and other complications after heart transplantation in patients taking amiodarone before surgery versus those not taking amiodarone. Author(s): Blomberg PJ, Feingold AD, Denofrio D, Rand W, Konstam MA, Estes NA 3rd, Link MS. Source: The American Journal of Cardiology. 2004 February 1; 93(3): 379-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759399

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Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland. Author(s): Kurnik D, Loebstein R, Farfel Z, Ezra D, Halkin H, Olchovsky D. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2004 March; 83(2): 107-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15028964

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Concentration dependent mitochondrial effect of amiodarone. Author(s): Varbiro G, Toth A, Tapodi A, Veres B, Sumegi B, Gallyas F Jr. Source: Biochemical Pharmacology. 2003 April 1; 65(7): 1115-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663047

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Concentration response relationships of amiodarone and desethylamiodarone. Author(s): Connolly SJ, Gupta RN, Hoffert D, Roberts RS. Source: American Heart Journal. 1988 June; 115(6): 1208-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3376838

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Conversion of recent-onset atrial fibrillation or flutter with ibutilide after amiodarone has failed. Author(s): Hennersdorf MG, Perings SM, Zuhlke C, Heidland UE, Perings C, Heintzen MP, Strauer BE. Source: Intensive Care Medicine. 2002 July; 28(7): 925-9. Epub 2002 May 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12122531

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Conversion of recent-onset atrial fibrillation with intravenous amiodarone: a metaanalysis of randomized controlled trials. Author(s): Hilleman DE, Spinler SA. Source: Pharmacotherapy. 2002 January; 22(1): 66-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794432

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Conversion of rheumatic atrial fibrillation by amiodarone after percutaneous balloon mitral commissurotomy. Author(s): Liu TJ, Hsueh CW, Lee WL, Lai HC, Wang KY, Ting CT. Source: The American Journal of Cardiology. 2003 November 15; 92(10): 1244-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609612

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Cost-effectiveness of targeting patients undergoing cardiac surgery for therapy with intravenous amiodarone to prevent atrial fibrillation. Author(s): Mahoney EM, Thompson TD, Veledar E, Williams J, Weintraub WS. Source: Journal of the American College of Cardiology. 2002 August 21; 40(4): 737-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12204505

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Delayed development of amiodarone keratopathy in a corneal graft. Author(s): Davitt SP, Mannis MJ. Source: Cornea. 1997 November; 16(6): 695-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9395883

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Depressed heart rate variability identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone: a substudy of EMIAT (The European Myocardial Infarct Amiodarone Trial). Author(s): Malik M, Camm AJ, Janse MJ, Julian DG, Frangin GA, Schwartz PJ. Source: Journal of the American College of Cardiology. 2000 April; 35(5): 1263-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10758969

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Determination of amiodarone and desethylamiodarone in human plasma by highperformance liquid chromatography-electrospray ionization tandem mass spectrometry with an ion trap detector. Author(s): Kollroser M, Schober C. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 January 25; 766(2): 219-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11824809

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Development of an enzyme-linked immunosorbent assay for the quantification of amiodarone. Author(s): Saita T, Fujito H, Mori M. Source: Biological & Pharmaceutical Bulletin. 2002 August; 25(8): 954-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12186425

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Development of severe adverse effects after discontinuing amiodarone therapy in human heart transplant recipients. Author(s): Preuner JG, Lehle K, Keyser A, Merk J, Rupprecht L, Goebels R. Source: Transplantation Proceedings. 1998 December; 30(8): 3943-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9865253

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Diagnosis of amiodarone pulmonary toxicity with high-resolution computerized tomographic scan. Author(s): Siniakowicz RM, Narula D, Suster B, Steinberg JS. Source: Journal of Cardiovascular Electrophysiology. 2001 April; 12(4): 431-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11332563

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Diagnostic accuracy of KL-6 as a marker of amiodarone-induced pulmonary toxicity. Author(s): Endoh Y, Hanai R, Uto K, Tanaka T, Ohta Y, Kasanuki H, Ohnishi S. Source: Pacing and Clinical Electrophysiology : Pace. 2000 November; 23(11 Pt 2): 20103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11139980

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Differential diagnosis and clinical course of amiodarone-induced thyroid dysfunction. Author(s): Alyan O, Arda K, Ozdemir O, Acu B, Soylu M, Demirkan D. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 September; 9(9): Pi117-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960935

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Difficult cases in heart failure: amiodarone lung injury: another heart failure mimic? Author(s): Sangha S, Uber PA, Mehra MR. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 March-April; 8(2): 93-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927785

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Digitoxin intoxication during concomitant use of amiodarone. Author(s): Laer S, Scholz H, Buschmann I, Thoenes M, Meinertz T. Source: European Journal of Clinical Pharmacology. 1998 March; 54(1): 95-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9591938

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Digoxin, flecainide, and amiodarone transfer across the placenta and the effects of an elevated umbilical venous pressure on the transfer rate. Author(s): Schmolling J, Renke K, Richter O, Pfeiffer K, Schlebusch H, Holler T. Source: Therapeutic Drug Monitoring. 2000 October; 22(5): 582-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11034264

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Disposition of intravenous amiodarone in subjects with normal and impaired renal function. Author(s): Ujhelyi MR, Klamerus KJ, Vadiei K, O'Rangers E, Izard M, Neefe DL, Zimmerman JJ, Chow MS. Source: Journal of Clinical Pharmacology. 1996 February; 36(2): 122-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8852388

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Dose of amiodarone in atrial fibrillation - neither guidelines nor clinical practice reflect available evidence. Author(s): Blackman DJ, Ferguson JD, Bashir Y. Source: European Heart Journal. 2002 June; 23(11): 908. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042013

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Dose-dependent appearance and disappearance of amiodarone-induced skin pigmentation. Author(s): Kounis NG, Frangides C, Papadaki PJ, Zavras GM, Goudevenos J. Source: Clin Cardiol. 1996 July; 19(7): 592-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8818442

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Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias. The Intravenous Amiodarone Multicenter Investigators Group. Author(s): Scheinman MM, Levine JH, Cannom DS, Friehling T, Kopelman HA, Chilson DA, Platia EV, Wilber DJ, Kowey PR. Source: Circulation. 1995 December 1; 92(11): 3264-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7586313

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Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Author(s): Libersa CC, Brique SA, Motte KB, Caron JF, Guedon-Moreau LM, Humbert L, Vincent A, Devos P, Lhermitte MA. Source: British Journal of Clinical Pharmacology. 2000 April; 49(4): 373-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10759694

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Drug-induced lupus erythematosus by amiodarone. Author(s): Sheikhzadeh A, Schafer U, Schnabel A. Source: Archives of Internal Medicine. 2002 April 8; 162(7): 834-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926860

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Drugs to promote sinus rhythm reversion and maintenance in atrial fibrillation--why amiodarone is better. Author(s): Nattel S. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2003 January; 17(1): 5-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916518

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Dual chamber pacing in patients with severe heart failure on beta blocker and amiodarone treatment: preliminary results of a randomised study. Author(s): Nagele H, Schomburg R, Petersen B, Rodiger W. Source: Heart (British Cardiac Society). 2002 June; 87(6): 566-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010943

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Duration of preoperative amiodarone treatment may be associated with postoperative hospital mortality in patients undergoing heart transplantation. Author(s): Chin C, Feindel C, Cheng D. Source: Journal of Cardiothoracic and Vascular Anesthesia. 1999 October; 13(5): 562-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10527225

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Early recurrence of arrhythmia in patients taking amiodarone or class 1C agents for treatment of atrial fibrillation or atrial flutter. Author(s): Hauser TH, Pinto DS, Josephson ME, Zimetbaum P. Source: The American Journal of Cardiology. 2004 May 1; 93(9): 1173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15110217

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Effect of amiodarone +/- diltiazem +/- beta blocker on frequency of atrial fibrillation, length of hospitalization, and hospital costs after coronary artery bypass grafting. Author(s): Kim MH, Rachwal W, McHale C, Bruckman D, Decena BF, Russman P, Morady F, Eagle KA. Source: The American Journal of Cardiology. 2002 May 1; 89(9): 1126-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988208

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Effect of amiodarone on dispersion of atrial refractoriness and cycle length in patients with atrial fibrillation. Author(s): Fynn SP, Todd DM, Hobbs WJ, Armstrong KL, Fitzpatrick AP, Garratt CJ. Source: Journal of Cardiovascular Electrophysiology. 2003 May; 14(5): 485-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776865

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Effect of amiodarone on the descending limb of the T wave. Author(s): Smetana P, Pueyo E, Hnatkova K, Batchvarov V, Camm AJ, Malik M. Source: The American Journal of Cardiology. 2003 September 15; 92(6): 742-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972125

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Effect of low-dose amiodarone on atrial fibrillation or flutter in Japanese patients with heart failure. Author(s): Shiga T, Wakaumi M, Imai T, Suzuki T, Hosaka F, Yamada Y, Matsuda N, Shoda M, Sugiura R, Hagiwara N, Kasanuki H. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 June; 66(6): 600-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074281

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Effect of right atrial pacing, intravenous amiodarone and beta blockers for suppression of atrial fibrillation after coronary artery bypass surgery: a pilot study. Author(s): Cardona F, Seide H, Cox RA, Perez CM. Source: P R Health Sci J. 2003 June; 22(2): 119-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12866134

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Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation. Author(s): Peuhkurinen K, Niemela M, Ylitalo A, Linnaluoto M, Lilja M, Juvonen J. Source: The American Journal of Cardiology. 2000 February 15; 85(4): 462-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10728951

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Effectiveness of amiodarone for conversion of atrial fibrillation to sinus rhythm: a meta-analysis. Author(s): Letelier LM, Udol K, Ena J, Weaver B, Guyatt GH. Source: Archives of Internal Medicine. 2003 April 14; 163(7): 777-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695268

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Effectiveness of amiodarone therapy in patients with severe congestive heart failure and intolerance to metoprolol. Author(s): Anastasiou-Nana MI, Margari ZJ, Terrovitis JV, Rapti AC, Alexopoulos GP, Nanas JN. Source: The American Journal of Cardiology. 2002 November 1; 90(9): 1017-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398977

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Effects of amiodarone and diltiazem on persistent atrial fibrillation conversion and recurrence rates: a randomized controlled study. Author(s): Manios EG, Mavrakis HE, Kanoupakis EM, Kallergis EM, Dermitzaki DN, Kambouraki DC, Vardas PE. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2003 January; 17(1): 31-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843685

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Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. Author(s): Lalevee N, Nargeot J, Barrere-Lemaire S, Gautier P, Richard S. Source: Journal of Cardiovascular Electrophysiology. 2003 August; 14(8): 885-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890054

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Effects of isoproterenol and amiodarone on the double potential interval after ablation of the cavotricuspid isthmus. Author(s): Tada H, Ozaydin M, Chugh A, Scharf C, Oral H, Pelosi F Jr, Knight BP, Strickberger SA, Morady F. Source: Journal of Cardiovascular Electrophysiology. 2003 September; 14(9): 935-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950537

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Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers. Author(s): Zhi J, Moore R, Kanitra L, Mulligan TE. Source: Journal of Clinical Pharmacology. 2003 April; 43(4): 428-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12723464

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Effects of therapy with amiodarone on clinical, functional, and cardiac sympathetic innervation in patients with idiopathic dilated cardiomyopathy. Author(s): Flotats A, Carrio I. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2004 March-April; 11(2): 110-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15052240

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Efficacy and safety of intravenous amiodarone for incessant tachycardias in infants. Author(s): Burri S, Hug MI, Bauersfeld U. Source: European Journal of Pediatrics. 2003 December; 162(12): 880-4. Epub 2003 September 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508682

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Efficacy of amiodarone for the termination of chronic atrial fibrillation and maintenance of normal sinus rhythm: a prospective, multicenter, randomized, controlled, double blind trial. Author(s): Galperin J, Elizari MV, Chiale PA, Molina RT, Ledesma R, Scapin AO, Vazquez Blanco M; GEFCA Investigators-GEMA Group, Buenos Aires, Argentina. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2001 October; 6(4): 341-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907636

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Efficacy of amiodarone treatment on cardiac symptom, function, and sympathetic nerve activity in patients with dilated cardiomyopathy: comparison with beta-blocker therapy. Author(s): Toyama T, Hoshizaki H, Seki R, Isobe N, Adachi H, Naito S, Oshima S, Taniguchi K. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2004 March-April; 11(2): 134-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15052244

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Electrical storm due to amiodarone induced thyrotoxicosis in a young adult with dilated cardiomyopathy: thyroidectomy as the treatment of choice. Author(s): Marketou ME, Simantirakis EN, Manios EG, Vardas PE. Source: Pacing and Clinical Electrophysiology : Pace. 2001 December; 24(12): 1827-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817822

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Electrophysiologically guided amiodarone therapy versus the implantable cardioverter-defibrillator for sustained ventricular tachyarrhythmias after myocardial infarction: results of long-term follow-up. Author(s): Schlapfer J, Rapp F, Kappenberger L, Fromer M. Source: Journal of the American College of Cardiology. 2002 June 5; 39(11): 1813-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12039497

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Exfoliative dermatitis after amiodarone treatment. Author(s): Moots RJ, Banerjee A. Source: British Medical Journal (Clinical Research Ed.). 1988 May 7; 296(6632): 1332-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2968133

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Failure of amiodarone to prevent ventricular fibrillation (sudden death) in hypertrophic cardiomyopathy. Author(s): Mercereau D, Kubac G, Klinke WP. Source: The Canadian Journal of Cardiology. 1989 March; 5(2): 77-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2706577

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Failure of plasmapheresis, corticosteroids and thionamides to ameliorate a case of protracted amiodarone-induced thyroiditis. Author(s): Samaras K, Marel GM. Source: Clinical Endocrinology. 1996 September; 45(3): 365-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8949576

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Failure to control hyperthyroidism with a thionamide after KClO4 withdrawal in a patient with amiodarone associated thyrotoxicosis. Author(s): De Weweire A, Unger P, Delwiche F, Unger J. Source: J Endocrinol Invest. 1987 October; 10(5): 529-30. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2828459

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Failure to respond to dexamethasone with fatal consequences, after initial response to multidrug treatment in a case of amiodarone-associated thyrotoxicosis. Author(s): Peche R, Abramowicz M, Unger J. Source: The American Journal of Medicine. 1992 December; 93(6): 702-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1466370

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Fatal amiodarone hepatoxicity. Author(s): Gilinsky NH, Briscoe GW, Kuo CS. Source: The American Journal of Gastroenterology. 1988 February; 83(2): 161-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3341340

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Fatal fulminating liver failure possibly related to amiodarone treatment. Author(s): Lwakatare JM, Morris-Jones S, Knight EJ. Source: Br J Hosp Med. 1990 July; 44(1): 60-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2397338

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Fatal hepatic failure due to prolonged amiodarone treatment. Author(s): Snir Y, Pick N, Riesenberg K, Yanai-Inbar I, Zirkin H, Schlaeffer F. Source: Journal of Clinical Gastroenterology. 1995 April; 20(3): 265-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7797846

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Fatal hepatotoxicity following oral administration of amiodarone. Author(s): Richer M, Robert S. Source: The Annals of Pharmacotherapy. 1995 June; 29(6): 582-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7663029

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Fatal hyperthyroidism after amiodarone treatment and total lymphoid irradiation in a heart transplant recipient. Author(s): Hauptman PJ, Fyfe B, Mechanick J, Lansman S, Gass A. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1993 May-June; 12(3): 513-6. Erratum In: J Heart Lung Transplant 1993 July-August; 12(4): 572. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8329429

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Fatal postoperative amiodarone pulmonary toxicity. Author(s): Kay GN, Epstein AE, Kirklin JK, Diethelm AG, Graybar G, Plumb VJ. Source: The American Journal of Cardiology. 1988 September 1; 62(7): 490-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3414530

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Fatal pulmonary toxicity occurring within two weeks of initiation of amiodarone. Author(s): Kharabsheh S, Abendroth CS, Kozak M. Source: The American Journal of Cardiology. 2002 April 1; 89(7): 896-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11909587

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Features of amiodarone-induced optic neuropathy. Author(s): Macaluso DC, Shults WT, Fraunfelder FT. Source: American Journal of Ophthalmology. 1999 May; 127(5): 610-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10334361

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Fetal and neonatal adverse effects profile of amiodarone treatment during pregnancy. Author(s): Widerhorn J, Bhandari AK, Bughi S, Rahimtoola SH, Elkayam U. Source: American Heart Journal. 1991 October; 122(4 Pt 1): 1162-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1927869

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Fetal hypothyroidism as a complication of amiodarone treatment for persistent fetal supraventricular tachycardia. Author(s): De Catte L, De Wolf D, Smitz J, Bougatef A, De Schepper J, Foulon W. Source: Prenatal Diagnosis. 1994 August; 14(8): 762-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7991517

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First clinical experience with the rapid-, short-acting amiodarone derivative E 047/1 after cardiac surgery. Author(s): Gombotz H, Vicenzi M, Mahla E, Rehak P, Metzler H. Source: European Journal of Anaesthesiology. 2002 January; 19(1): 23-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11913800

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Five-year follow-up of 589 patients treated with amiodarone. Author(s): Weinberg BA, Miles WM, Klein LS, Bolander JE, Dusman RE, Stanton MS, Heger JJ, Langefeld C, Zipes DP. Source: American Heart Journal. 1993 January; 125(1): 109-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8417505

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Flecainide acetate dose-concentration relationship in cardiac arrhythmias: influence of heart failure and amiodarone. Author(s): Leclercq JF, Denjoy I, Mentre F, Coumel P. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1990 August; 4(4): 1161-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2128031

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Flecainide and amiodarone: combined therapy for refractory tachyarrhythmias in infancy. Author(s): Fenrich AL Jr, Perry JC, Friedman RA. Source: Journal of the American College of Cardiology. 1995 April; 25(5): 1195-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7897134

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Frequency dependent effects of d-sotalol and amiodarone on the action potential duration of the human right ventricle. Author(s): Huikuri HV, Yli-Mayry S. Source: Pacing and Clinical Electrophysiology : Pace. 1992 November; 15(11 Pt 2): 21037. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1279607

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Frequency-dependent electrophysiologic effects of amiodarone in humans. Author(s): Sager PT, Uppal P, Follmer C, Antimisiaris M, Pruitt C, Singh BN. Source: Circulation. 1993 September; 88(3): 1063-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8353868

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Ga-67 imaging of amiodarone pulmonary toxicity with pseudocavitary lung lesion. Author(s): Nguyen BD, Isaacs GH, Alhakim N, Yakulis R. Source: Clinical Nuclear Medicine. 1992 June; 17(6): 507-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1617851

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Gallium lung scintigraphy in amiodarone pulmonary toxicity. Author(s): Zhu YY, Botvinick E, Dae M, Golden J, Hattner R, Scheinman M. Source: Chest. 1988 June; 93(6): 1126-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3371091

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Gallium scintigraphy in the detection of amiodarone lung toxicity. Author(s): Moinuddin M, Rockett J. Source: Ajr. American Journal of Roentgenology. 1986 September; 147(3): 607-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3488662

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Gallium uptake in the thyroid gland in amiodarone-induced hyperthyroidism. Author(s): Ling MC, Dake MD, Okerlund MD. Source: Clinical Nuclear Medicine. 1988 April; 13(4): 258-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3163535

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Gallium-67 and pulmonary complications of amiodarone. Author(s): Lecklitner ML, Johnson DR, Hughes JJ. Source: Clinical Nuclear Medicine. 1988 November; 13(11): 826-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3233870

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Gallium-67 lung imaging and pulmonary clearance of 99mTc-DTPA aerosol in patients with amiodarone pneumonitis. Author(s): Terra-Filho M, Meneghetti JC, Cukier A, Teixeira LR, Soares Junior J, Camargo EE, Vargas FS. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 1996 November; 29(11): 1467-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9196547

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Gastrointestinal case of the day. Hepatic and pulmonary accumulation of amiodarone. Author(s): Hopper KD, Potok PS. Source: Ajr. American Journal of Roentgenology. 1994 June; 162(6): 1449-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8192017

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Goiter and hypothyroidism during re-treatment with amiodarone in a patient who previously experienced amiodarone-induced thyrotoxicosis. Author(s): Kaplan J, Ish-Shalom S. Source: The American Journal of Medicine. 1991 June; 90(6): 750-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2042691

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Granular cells as a marker of early amiodarone hepatotoxicity. Author(s): Jain D, Bowlus CL, Anderson JM, Robert ME. Source: Journal of Clinical Gastroenterology. 2000 October; 31(3): 241-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11034006

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Granular cells as a marker of early amiodarone hepatotoxicity: a pathological and analytical study. Author(s): Shepherd NA, Dawson AM, Crocker PR, Levison DA. Source: Journal of Clinical Pathology. 1987 April; 40(4): 418-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3584485

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Heart rate is a marker of amiodarone mortality reduction in severe heart failure. The GESICA-GEMA Investigators. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina-Grupo de Estudios Multicentricos en Argentina. Author(s): Nul DR, Doval HC, Grancelli HO, Varini SD, Soifer S, Perrone SV, Prieto N, Scapin O. Source: Journal of the American College of Cardiology. 1997 May; 29(6): 1199-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9137213

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Hemodynamic and surface electrocardiographic effects of a new aqueous formulation of intravenous amiodarone. Author(s): Gallik DM, Singer I, Meissner MD, Molnar J, Somberg JC. Source: The American Journal of Cardiology. 2002 November 1; 90(9): 964-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398963

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Hemodynamics during chronic amiodarone administration in Japanese patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia: a retrospective study. Author(s): Suzuki T, Shiga T, Wakaumi M, Matsuda N, Ishizuka N, Kasanuki H. Source: J Cardiol. 2003 April; 41(4): 169-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12728537

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Hepatotoxicity of amiodarone. Author(s): Jeyamalar R, Pathmanathan R, Wong D, Kannan P. Source: Ann Acad Med Singapore. 1992 November; 21(6): 838-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1295429

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Heterogeneity of amiodarone-induced thyrotoxicosis: evaluation of colour-flow Doppler sonography in predicting therapeutic response. Author(s): Wong R, Cheung W, Stockigt JR, Topliss DJ. Source: Internal Medicine Journal. 2003 September-October; 33(9-10): 420-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511194

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High defibrillation threshold at cardioverter defibrillator implantation under amiodarone treatment: favorable effects of D, L-sotalol. Author(s): Boriani G, Biffi M, Frabetti L, Maraschi M, Branzi A. Source: Heart & Lung : the Journal of Critical Care. 2000 November-December; 29(6): 412-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11080321

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High dose oral amiodarone loading exerts important hemodynamic actions in patients with congestive heart failure. Author(s): Gottlieb SS, Riggio DW, Lauria S, Peters RW, Shorofsky SR, Cines M, Froman D, Gold MR. Source: Journal of the American College of Cardiology. 1994 March 1; 23(3): 560-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8113534

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High dose oral amiodarone loading: electrophysiologic effects and clinical tolerance. Author(s): Evans SJ, Myers M, Zaher C, Simonson J, Nalos P, Vaughn C, Oseran D, Gang E, Peter T, Mandel W. Source: Journal of the American College of Cardiology. 1992 January; 19(1): 169-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1729329

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High prevalence of thyroid dysfunction in adult patients with beta-thalassemia major submitted to amiodarone treatment. Author(s): Mariotti S, Loviselli A, Murenu S, Sau F, Valentino L, Mandas A, Vacquer S, Martino E, Balestrieri A, Lai ME. Source: J Endocrinol Invest. 1999 January; 22(1): 55-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10090138

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High-performance liquid chromatographic assay for amiodarone N-deethylation activity in human liver microsomes using solid-phase extraction. Author(s): Hanioka N, Saito Y, Soyama A, Ando M, Ozawa S, Sawada J. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 July 5; 774(1): 105-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12052728

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High-performance liquid chromatography assay of amiodarone in rat plasma. Author(s): Jun AS, Brocks DR. Source: Journal of Pharmacy & Pharmaceutical Sciences [electronic Resource] : a Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques. 2001 September-December; 4(3): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11737993

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HLA-B40-, HLA-Cw3-, and HLA-DR5-associated susceptibility to amiodaroneinduced thyroid dysfunction. Author(s): Erdogan MF, Gulec S, Tutar E, Guldal M, Baskal N, Erdogan G. Source: Thyroid : Official Journal of the American Thyroid Association. 2000 April; 10(4): 369-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10807068

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HRCT findings of amiodarone pulmonary toxicity: clinical and radiologic regression. Author(s): Poll LW, May P, Koch JA, Hetzel G, Heering P, Modder U. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2001 July; 6(3): 30711. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11584337

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Human experience with amiodarone in the embryonic period. Author(s): Ovadia M, Brito M, Hoyer GL, Marcus FI. Source: The American Journal of Cardiology. 1994 February 1; 73(4): 316-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8093128

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Hyperkalemia probably reverses the antiarrhythmic effects of amiodarone: a case report. Author(s): Akiyama J, Tomizawa T, Umezawa S, Morishima A. Source: Japanese Circulation Journal. 1999 April; 63(4): 323-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10475784

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Hypertrophic cardiomyopathy with massive hypertrophy, amiodarone treatment and high defibrillation threshold at cardioverter-defibrillator implant. Author(s): Boriani G, Rapezzi C, Biffi M, Branzi A. Source: International Journal of Cardiology. 2002 May; 83(2): 171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12007691

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Hypertrophic cardiomyopathy: is there a role for amiodarone? Author(s): Prasad K, Frenneaux MP. Source: Heart (British Cardiac Society). 1998 April; 79(4): 317-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9616334

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Hypomelanosis due to block of melanosomal maturation in amiodarone-induced hyperpigmentation. Author(s): Haas N, Schadendorf D, Hermes B, Henz BM. Source: Archives of Dermatology. 2001 April; 137(4): 513-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295949

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Hyponatremia during therapy with amiodarone. Author(s): Odeh M, Schiff E, Oliven A. Source: Archives of Internal Medicine. 1999 November 22; 159(21): 2599-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10573050

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Ibutilide versus amiodarone in atrial fibrillation: a double-blinded, randomized study. Author(s): Bernard EO, Schmid ER, Schmidlin D, Scharf C, Candinas R, Germann R. Source: Critical Care Medicine. 2003 April; 31(4): 1031-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682468

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Images in clinical medicine. Pigmentation related to amiodarone. Author(s): High WA, Weiss SD. Source: The New England Journal of Medicine. 2001 November 15; 345(20): 1464. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794195

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Improved survival of cardiac transplantation candidates with implantable cardioverter defibrillator therapy: role of beta-blocker or amiodarone treatment. Author(s): Ermis C, Zadeii G, Zhu AX, Fabian W, Collins J, Lurie KG, Sakaguchi S, Benditt DG. Source: Journal of Cardiovascular Electrophysiology. 2003 June; 14(6): 578-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875416

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In vivo confocal microscopy of patients with amiodarone-induced keratopathy. Author(s): Grupcheva CN, McGhee CN. Source: Cornea. 2002 May; 21(4): 430; Author Reply 430-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11973398

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In vivo confocal microscopy of patients with amiodarone-induced keratopathy. Author(s): Ciancaglini M, Carpineto P, Zuppardi E, Nubile M, Doronzo E, Mastropasqua L. Source: Cornea. 2001 May; 20(4): 368-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11333323

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Indicators of atrial fibrillation risk in cardiac surgery patients on prophylactic amiodarone. Author(s): Kalus JS, White CM, Caron MF, Coleman CI, Takata H, Kluger J. Source: The Annals of Thoracic Surgery. 2004 April; 77(4): 1288-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15063253

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Induction of c-jun and TGF-beta 1 in Fischer 344 rats during amiodarone-induced pulmonary fibrosis. Author(s): Chung WH, Bennett BM, Racz WJ, Brien JF, Massey TE. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2001 November; 281(5): L1180-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11597910

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Influence of amiodarone on urinary excretion of 6beta-hydroxycortisol in humans. Author(s): Micuda S, Hodac M, Sispera L, Parizek P, Pleskot M, Zimova G, Cerman J, Martinkova J, Pidrman V. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2001; 50(2): 191-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522047

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Inhibitory effect of bepridil on hKv1.5 channel current: comparison with amiodarone and E-4031. Author(s): Kobayashi S, Reien Y, Ogura T, Saito T, Masuda Y, Nakaya H. Source: European Journal of Pharmacology. 2001 November 2; 430(2-3): 149-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711026

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Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Author(s): Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T. Source: British Journal of Clinical Pharmacology. 2000 March; 49(3): 244-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10718780

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Intravenous amiodarone and off-pump coronary artery bypass graft procedures: a new role for intraoperative antiarrhythmic therapy? Author(s): Balser JR. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2001 October; 15(5): 542-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687990

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Intravenous amiodarone decreases the duration of atrial fibrillation associated with acute myocardial infarction. Author(s): Kontoyannis DA, Anastasiou-Nana MI, Kontoyannis SA, Zaga AK, Nanas JN. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2001 March; 15(2): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11669409

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Intravenous amiodarone for cardioversion of recent-onset atrial fibrillation. Author(s): Cybulski J, Kulakowski P, Budaj A, Danielewicz H, Maciejewicz J, KawkaUrbanek T, Ceremuzynski L. Source: Clin Cardiol. 2003 July; 26(7): 329-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12862299

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Intravenous amiodarone in intensive care: time for a reappraisal? Author(s): James PR, Barrera Groba C. Source: Intensive Care Medicine. 2001 August; 27(8): 1433. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11511965

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Intravenous lidocaine versus intravenous amiodarone (in a new aqueous formulation) for incessant ventricular tachycardia. Author(s): Somberg JC, Bailin SJ, Haffajee CI, Paladino WP, Kerin NZ, Bridges D, Timar S, Molnar J; Amio-Aqueous Investigators. Source: The American Journal of Cardiology. 2002 October 15; 90(8): 853-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372573

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Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: the Atrial Fibrillation Suppression Trial II (AFIST II). Author(s): White CM, Caron MF, Kalus JS, Rose H, Song J, Reddy P, Gallagher R, Kluger J; Atrial Fibrillation Suppression Trial II. Source: Circulation. 2003 September 9; 108 Suppl 1: Ii200-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970233

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Is amiodarone an underrecognized cause of acute respiratory failure in the ICU? Author(s): Ashrafian H, Davey P. Source: Chest. 2001 July; 120(1): 275-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11451849

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Is amiodarone the first or the last choice for the maintenance of sinus rhythm after successful conversion of atrial fibrillation? Author(s): Veloso HH. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2001 May-June; 7(3): 526-7; Author Reply 528-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386035

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Is it time to choose amiodarone for postoperative atrial fibrillation? Author(s): Saltman AE. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 June; 125(6): 1202-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830035

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Ischemia versus amiodarone induced polymorphic ventricular tachycardia. Author(s): Sharma H, Sharma N, Burke JF, Yan GX, Kowey PR. Source: Pacing and Clinical Electrophysiology : Pace. 2002 September; 25(9): 1382-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12380775

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KL-6 as a potential new marker for amiodarone-induced pulmonary toxicity. Author(s): Endoh Y, Hanai R, Uto K, Uno M, Nagashima H, Narimatsu A, Takizawa T, Onishi S, Kasanuki H. Source: The American Journal of Cardiology. 2000 July 15; 86(2): 229-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10913491

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KL-6 as a serum marker for amiodarone-induced pulmonary toxicity. Author(s): Kohno N, Yokoyama A, Kondo K. Source: Intern Med. 2000 December; 39(12): 1004-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197780

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Lack of a hypotensive effect with rapid administration of a new aqueous formulation of intravenous amiodarone. Author(s): Somberg JC, Timar S, Bailin SJ, Lakatos F, Haffajee CI, Tarjan J, Paladino WP, Sarosi I, Kerin NZ, Borbola J, Bridges DE, Molnar J; Amio-Aqueous Investigators. Source: The American Journal of Cardiology. 2004 March 1; 93(5): 576-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996582

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Lack of interaction between amiodarone and mexiletine in cardiac arrhythmia patients. Author(s): Yonezawa E, Matsumoto K, Ueno K, Tachibana M, Hashimoto H, Komamura K, Kamakura S, Miyatake K, Tanaka K. Source: Journal of Clinical Pharmacology. 2002 March; 42(3): 342-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11865972

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Late sodium current is a novel target for amiodarone: studies in failing human myocardium. Author(s): Maltsev VA, Sabbah HN, Undrovinas AI. Source: Journal of Molecular and Cellular Cardiology. 2001 May; 33(5): 923-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343415

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Life-threatening thyrotoxicosis induced by amiodarone in patients with benign heart disease. Author(s): Georges JL, Normand JP, Lenormand ME, Schwob J. Source: European Heart Journal. 1992 January; 13(1): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1577019

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Long-term amiodarone therapy and the risk of complications after cardiac surgery: results from the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT). Author(s): Crystal E, Kahn S, Roberts R, Thorpe K, Gent M, Cairns JA, Dorian P, Connolly SJ. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 March; 125(3): 633-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658206

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Long-term efficacy and toxicity of high- and low-dose amiodarone regimens. Author(s): Kerin NZ, Aragon E, Faitel K, Frumin H, Rubenfire M. Source: Journal of Clinical Pharmacology. 1989 May; 29(5): 418-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2661600

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Long-term efficacy of empirical chronic amiodarone therapy in patients with sustained ventricular tachyarrhythmia and structural heart disease. Author(s): Aiba T, Kurita T, Taguchi A, Shimizu W, Suyama K, Aihara N, Kamakura S. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 April; 66(4): 367-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11954951

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Long-term follow-up of patients requiring intravenous amiodarone to suppress hemodynamically destabilizing ventricular arrhythmias. Author(s): Fogel RI, Herre JM, Kopelman HA, Kowey PR, Trohman RG, Fineberg N, Prystowsky EN. Source: American Heart Journal. 2000 April; 139(4): 690-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10740153

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Long-term intermittent dobutamine infusion combined with oral amiodarone improves the survival of patients with severe congestive heart failure. Author(s): Nanas JN, Kontoyannis DA, Alexopoulos GP, Anastasiou-Nana MI, Tsagalou EP, Stamatelopoulos SF, Moulopoulos SD. Source: Chest. 2001 April; 119(4): 1173-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11296186

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Long-term intermittent dobutamine infusion, combined with oral amiodarone for end-stage heart failure: a randomized double-blind study. Author(s): Nanas JN, Tsagalou EP, Kanakakis J, Nanas SN, Terrovitis JV, Moon T, Anastasiou-Nana MI. Source: Chest. 2004 April; 125(4): 1198-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078725

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Long-term maintenance of normal sinus rhythm in patients with current symptomatic atrial fibrillation: amiodarone vs propafenone, both in low doses. Author(s): Kochiadakis GE, Igoumenidis NE, Hamilos MI, Tzerakis PG, Klapsinos NC, Zacharis EA, Vardas PE. Source: Chest. 2004 February; 125(2): 377-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769712

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Lopanoic acid rapidly controls type I amiodarone-induced thyrotoxicosis prior to thyroidectomy. Author(s): Bogazzi F, Aghini-Lombardi F, Cosci C, Lupi I, Santini F, Tanda ML, Miccoli P, Basolo F, Pinchera A, Bartalena L, Braverman LE, Martino E. Source: J Endocrinol Invest. 2002 February; 25(2): 176-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11929091

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Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study. Author(s): Kochiadakis GE, Igoumenidis NE, Marketou ME, Kaleboubas MD, Simantirakis EN, Vardas PE. Source: Heart (British Cardiac Society). 2000 September; 84(3): 251-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10956284

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Low dose amiodarone causing pseudo-alcoholic cirrhosis. Author(s): Singhal A, Ghosh P, Khan SA. Source: Age and Ageing. 2003 March; 32(2): 224-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615569

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Low dose amiodarone in refractory tachyarrhythmias. Author(s): Panja M, Maity AK, Kar AK, Chatterjee SS, Kumar S, Roy S, Sinha DP, Majumdar B, Panja S. Source: Indian Heart J. 1992 January-February; 44(1): 47-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1398696

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Low dose amiodarone pulmonary toxicity in a patient with a history of pneumonectomy. Author(s): van der Zeyden H, Zandstra D, van Hengstum M. Source: Intensive Care Medicine. 1992; 18(7): 422-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1469181

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Low-dose amiodarone for patients with advanced heart failure who are intolerant of beta-blockers. Author(s): Takemura K, Yasumura Y, Hirooka K, Hanatani A, Nakatani S, Komamura K, Yamagishi M, Miyatake K. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 May; 66(5): 441-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030336

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Low-dose amiodarone for the treatment of arrhythmias in hypertrophic cardiomyopathy. Author(s): Counihan PJ, McKenna WJ. Source: Journal of Clinical Pharmacology. 1989 May; 29(5): 436-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2661603

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Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Author(s): Kochiadakis GE, Igoumenidis NE, Marketou ME, Solomou MC, Kanoupakis EM, Vardas PE. Source: The American Journal of Cardiology. 1998 April 15; 81(8): 995-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9576159

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Low-dose oral amiodarone prophylaxis reduces atrial fibrillation after pulmonary resection. Author(s): Lanza LA, Visbal AI, DeValeria PA, Zinsmeister AR, Diehl NN, Trastek VF. Source: The Annals of Thoracic Surgery. 2003 January; 75(1): 223-30; Discussion 230. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12537220

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Major clinical trials assessing the prophylactic use of amiodarone in patients with ventricular tachyarrhythmias. Author(s): Fogoros RN. Source: Controlled Clinical Trials. 1996 June; 17(3 Suppl): 37S-46S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8877266

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Management of amiodarone-induced thyrotoxicosis. Author(s): Rajeswaran C, Shelton RJ, Gilbey SG. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2003 November 22; 133(43-44): 579-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745652

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Management of amiodarone-induced thyrotoxicosis. Author(s): Younis N, el-Houni A, Soran H, Jones IR. Source: Hosp Med. 2002 September; 63(9): 546-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12357858

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Management of persistent atrial fibrillation following balloon mitral valvotomy: safety and efficacy of low-dose amiodarone. Author(s): Kapoor A, Kumar S, Singh RK, Pandey CM, Sinha N. Source: J Heart Valve Dis. 2002 November; 11(6): 802-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479281

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Mechanisms underlying variability in response to drug therapy: implications for amiodarone use. Author(s): Roden DM. Source: The American Journal of Cardiology. 1999 November 4; 84(9A): 29R-36R. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10568657

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Meglumine antimoniate, amiodarone and torsades de pointes: a case report. Author(s): Segura I, Garcia-Bolao I. Source: Resuscitation. 1999 September; 42(1): 65-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10524732

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Men are at increased risk of amiodarone-associated thyrotoxicosis in the UK. Author(s): Sidhu J, Jenkins D. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 December; 96(12): 949-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631062

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Metabolism of amiodarone. II. High-performance liquid chromatographic assay for mono-N-desethylamiodarone hydroxylation in liver microsomes. Author(s): Ha HR, Kozlik P, Stieger B, Bigler L, Follath F. Source: J Chromatogr B Biomed Sci Appl. 2001 June 15; 757(2): 309-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11417876

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Microassay of amiodarone and desethylamiodarone in serum by capillary electrophoresis with head-column field-amplified sample stacking. Author(s): Zhang CX, Aebi Y, Thormann W. Source: Clinical Chemistry. 1996 November; 42(11): 1805-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8906080

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Monitoring may need to be prolonged in patients given warfarin and amiodarone. Author(s): Tomlinson B, Young RP, Chan TY, Critchley JA, Chan JC. Source: Bmj (Clinical Research Ed.). 1996 August 3; 313(7052): 301-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8704564

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Monitoring of hepatic function during amiodarone therapy. Author(s): Pollak PT, You YD. Source: The American Journal of Cardiology. 2003 March 1; 91(5): 613-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615276

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Morbidity and mortality following early administration of amiodarone in acute myocardial infarction. GEMICA study investigators, GEMA Group, Buenos Aires, Argentina. Grupo de Estudios Multicentricos en Argentina. Author(s): Elizari MV, Martinez JM, Belziti C, Ciruzzi M, Perez de la Hoz R, Sinisi A, Carbajales J, Scapin O, Garguichevich J, Girotti L, Cagide A. Source: European Heart Journal. 2000 February; 21(3): 198-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10639301

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More on amiodarone and torsade de pointes. Author(s): Ostermaier R, von Essen R. Source: Circulation. 1996 November 1; 94(9): 2316-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8901701

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More on amiodarone-induced depression. Author(s): Odelola AT. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1999 December; 175: 590-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10789368

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More on amiodarone--meeting the challenges of the combined epidemics of heart failure and atrial fibrillation? Author(s): Singh BN. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2003 September; 8(3): 175-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506541

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More on an infant with acute pulmonary toxicity during amiodarone therapy. Author(s): Birmingham WP. Source: The American Journal of Cardiology. 1998 May 1; 81(9): 1171. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9605063

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Mortality benefit of implantable cardioverter-defibrillator therapy in patients with persistent malignant ventricular arrhythmias despite amiodarone treatment. Author(s): Barron HV, Khan HH, Viskin S, Heller K, Kalman JM, Scheinman MM, Lesh MD. Source: The American Journal of Cardiology. 1997 May 1; 79(9): 1180-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9164881

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Mortality reduction by antiadrenergic modulation of arrhythmogenic substrate: significance of combining beta blockers and amiodarone. Author(s): Ogunyankin KO, Singh BN. Source: The American Journal of Cardiology. 1999 November 4; 84(9A): 76R-82R. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10568664

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Myocardial amiodarone concentrations after short- and long-term treatment in patients with end-stage heart failure. Author(s): Candinas R, Frielingsdorf J, Ha HR, Carrel T, Turina M, Follath F. Source: European Journal of Clinical Pharmacology. 1998 January; 53(5): 331-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9516032

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Myopathy and accumulation of amiodarone. Author(s): Carella F. Source: Muscle & Nerve. 1989 June; 12(6): 514. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2725579

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Near normalization of spirometry in a subject with severe emphysema complicated by amiodarone lung. Author(s): Cockcroft DW, Fisher KL. Source: Respiratory Medicine. 1999 August; 93(8): 597-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10542995

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Neonatal hyperthyroxinaemia associated with maternal amiodarone therapy: case report. Author(s): Tubman R, Jenkins J, Lim J. Source: Ir J Med Sci. 1988 July; 157(7): 243. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2459079

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Neonatal hypothyroidism after treatment by amiodarone during pregnancy. Author(s): Laurent M, Betremieux P, Biron Y, LeHelloco A. Source: The American Journal of Cardiology. 1987 October 1; 60(10): 942. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3661421

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Neonatal refractory supraventricular tachycardia: successful treatment with amiodarone. Author(s): Rosenberg EM, Elbl F, Solinger RE, Palakurthy P, Rees AH. Source: Southern Medical Journal. 1988 April; 81(4): 539-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3358183

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Neurodevelopment after in utero amiodarone exposure. Author(s): Magee LA, Nulman I, Rovet JF, Koren G. Source: Neurotoxicology and Teratology. 1999 May-June; 21(3): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10386829

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Neutropenia during treatment with amiodarone. Author(s): Groneberg DA, Barkhuizen A. Source: The American Journal of Medicine. 2001 June 1; 110(8): 671. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11388342

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New antiarrhythmic drugs in pediatric use: amiodarone. Author(s): Paul T, Guccione P. Source: Pediatric Cardiology. 1994 May-June; 15(3): 132-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8047495

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New antiarrhythmic drugs: tocainide, mexiletine, flecainide, encainide, and amiodarone. Author(s): Kreeger RW, Hammill SC. Source: Mayo Clinic Proceedings. 1987 November; 62(11): 1033-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3118116

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Noncardiac side-effects of long-term oral amiodarone in the elderly. Author(s): Hyatt RH, Sinha B, Vallon A, Bailey RJ, Martin A. Source: Age and Ageing. 1988 March; 17(2): 116-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3369337

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Nongoitrous (type I) amiodarone-associated thyrotoxicosis: evidence of follicular disruption in vitro and in vivo. Author(s): Brennan MD, Erickson DZ, Carney JA, Bahn RS. Source: Thyroid : Official Journal of the American Thyroid Association. 1995 June; 5(3): 177-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7580265

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Nonsustained polymorphous ventricular tachycardia during amiodarone therapy for atrial fibrillation complicating cardiomyopathy. Management with intravenous magnesium sulfate. Author(s): Winters SL, Sachs RG, Curwin JH. Source: Chest. 1997 May; 111(5): 1454-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9149614

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Nonsustained ventricular tachycardia as a predictor for sudden death in patients with idiopathic dilated cardiomyopathy. The role of amiodarone treatment. Author(s): Castelli G, Ciaccheri M, Cecchi F, Troiani V, Nannini M, Marconi P, Olivotto J, Montereggi A, Dolara A. Source: G Ital Cardiol. 1999 May; 29(5): 514-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10367218

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Normalization of peripheral thyroid hormone metabolism induced by successful chronic amiodarone treatment in patients with ventricular arrhythmias. Author(s): Iervasi G, Clerico A, Berti S, Pilo A, Biagini A, Bianchi R, Donato L. Source: European Journal of Clinical Investigation. 1996 May; 26(5): 382-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8796365

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Of pills and pillows: pseudopigmentation in a patient taking amiodarone. Author(s): Gutknecht DR. Source: Cutis; Cutaneous Medicine for the Practitioner. 2000 October; 66(4): 294. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11109154

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Optic neuropathy following amiodarone therapy. Author(s): Sreih AG, Schoenfeld MH, Marieb MA. Source: Pacing and Clinical Electrophysiology : Pace. 1999 July; 22(7): 1108-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10456646

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Optimizing oral dosing and monitoring of noncardiac toxicities with chronic amiodarone therapy. Author(s): Tsikouris JP, White CM, Kluger J. Source: Conn Med. 2000 January; 64(1): 35-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10697362

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Oral amiodarone and atrial fibrillation. Author(s): Routledge HC, Nuttall SL, Kendall MJ. Source: Lancet. 2001 July 14; 358(9276): 148-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469236

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Oral amiodarone and atrial fibrillation. Author(s): Tahapary GJ, Suttorp MJ. Source: Lancet. 2001 July 14; 358(9276): 147; Author Reply 148-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469235

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Oral amiodarone and atrial fibrillation. Author(s): Brilakis ES, Friedman PA, Gersh BJ, Shen WK. Source: Lancet. 2001 July 14; 358(9276): 147-8; Author Reply 148-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469234

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Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial. Author(s): Giri S, White CM, Dunn AB, Felton K, Freeman-Bosco L, Reddy P, Tsikouris JP, Wilcox HA, Kluger J. Source: Lancet. 2001 March 17; 357(9259): 830-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11265951

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Oral amiodarone loading therapy. I. The effect on serial signal-averaged electrocardiographic recordings and the QTc in patients with ventricular tachyarrhythmias. Author(s): Borbola J, Denes P. Source: American Heart Journal. 1988 June; 115(6): 1202-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3376837

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Organic anion transporter oatp2-mediated interaction between digoxin and amiodarone in the rat liver. Author(s): Kodawara T, Masuda S, Wakasugi H, Uwai Y, Futami T, Saito H, Abe T, Inu K. Source: Pharmaceutical Research. 2002 June; 19(6): 738-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12134942

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Outcome of thyroid function in newborns from mothers treated with amiodarone. Author(s): Matsumura LK, Born D, Kunii IS, Franco DB, Maciel RM. Source: Thyroid : Official Journal of the American Thyroid Association. 1992 Winter; 2(4): 279-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1493368

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Pharmacologic reversion of persistent atrial fibrillation with amiodarone predicts long-term sinus rhythm maintenance. Author(s): Galperin J, Elizari MV, Chiale PA, Molina RT, Ledesma R, Scapin AO, Blanco MV, Bonato R, Lago M; Grupo de Estudio de Fibrilacion Auricular Con Amiodarona (GEFACA) Investigators. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2003 September; 8(3): 179-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506542

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Pharmacological cardioversion of recent onset atrial fibrillation with intravenous amiodarone in patients receiving long-term amiodarone therapy: is it reasonable? Author(s): Kanoupakis EM, Kochiadakis GE, Manios EG, Igoumenidis NE, Mavrakis HE, Vardas PE. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2003 February; 8(1): 19-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12652173

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Post-discharge recurrences of new-onset atrial fibrillation following cardiac surgery: impact of low-dose amiodarone and beta-blocker prophylaxis. Author(s): Cioffi G, Cemin C, Russo TE, Pellegrini A, Terrasi F, Ferrario G. Source: Ital Heart J. 2000 October; 1(10): 691-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11061366

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Postoperative oral amiodarone as prophylaxis against atrial fibrillation after coronary artery surgery. Author(s): Yazigi A, Rahbani P, Zeid HA, Madi-Jebara S, Haddad F, Hayek G. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2002 October; 16(5): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407614

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Potential cost-effectiveness of prophylactic use of the implantable cardioverter defibrillator or amiodarone after myocardial infarction. Author(s): Sanders GD, Hlatky MA, Every NR, McDonald KM, Heidenreich PA, Parsons LS, Owens DK. Source: Annals of Internal Medicine. 2001 November 20; 135(10): 870-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11712877

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Preparation with iopanoic acid rapidly controls thyrotoxicosis in patients with amiodarone-induced thyrotoxicosis before thyroidectomy. Author(s): Bogazzi F, Miccoli P, Berti P, Cosci C, Brogioni S, Aghini-Lombardi F, Materazzi G, Bartalena L, Pinchera A, Braverman LE, Martino E. Source: Surgery. 2002 December; 132(6): 1114-7; Discussion 1118. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490863

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Prevention of atrial fibrillation after cardiac surgery: the significance of postoperative oral amiodarone. Author(s): Stamou SC, Hill PC, Sample GA, Snider E, Pfister AJ, Lowery RC, Corso PJ. Source: Chest. 2001 December; 120(6): 1936-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11742925

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Prospective evaluation of a discriminant function for prediction of recurrent symptomatic ventricular tachycardia or ventricular fibrillation in coronary artery disease patients receiving amiodarone and having inducible ventricular tachycardia at electrophysiologic study. Author(s): Klein LS, Fineberg N, Heger JJ, Miles WM, Kammerling JM, Chang MS, Zipes DP, Prystowsky EN. Source: The American Journal of Cardiology. 1988 May 1; 61(13): 1024-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3364357

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Pulmonary effects of low dose amiodarone: a review of the risks and recommendations for surveillance. Author(s): Sunderji R, Kanji Z, Gin K. Source: The Canadian Journal of Cardiology. 2000 November; 16(11): 1435-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11109040

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Pulmonary toxicity in patients receiving low-dose amiodarone. Author(s): Ott MC, Khoor A, Leventhal JP, Paterick TE, Burger CD. Source: Chest. 2003 February; 123(2): 646-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576397

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QT prolongation and polymorphous ventricular tachycardia associated with trasodone-amiodarone combination. Author(s): Mazur A, Strasberg B, Kusniec J, Sclarovsky S. Source: International Journal of Cardiology. 1995 November 10; 52(1): 27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8707432

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QT prolongation and the antiarrhythmic efficacy of amiodarone. Author(s): Torres V, Tepper D, Flowers D, Wynn J, Lam S, Keefe D, Miura DS, Somberg JC. Source: Journal of the American College of Cardiology. 1986 January; 7(1): 142-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3941202

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QT prolongation associated with azithromycin/amiodarone combination. Author(s): Samarendra P, Kumari S, Evans SJ, Sacchi TJ, Navarro V. Source: Pacing and Clinical Electrophysiology : Pace. 2001 October; 24(10): 1572-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11707055

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Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death. Author(s): Sim I, McDonald KM, Lavori PW, Norbutas CM, Hlatky MA. Source: Circulation. 1997 November 4; 96(9): 2823-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9386144

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Radioiodine ablation of the thyroid to allow the reintroduction of amiodarone treatment in patients with a prior history of amiodarone-induced thyrotoxicosis. Author(s): Hermida JS, Jarry G, Tcheng E, Moullart V, Arlot S, Rey JL, Delonca J, Schvartz C. Source: The American Journal of Medicine. 2004 March 1; 116(5): 345-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984821

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Rapid loading of sotalol or amiodarone for management of recent onset symptomatic atrial fibrillation: a randomized, digoxin-controlled trial. Author(s): Thomas SP, Guy D, Wallace E, Crampton R, Kijvanit P, Eipper V, Ross DL, Cooper MJ. Source: American Heart Journal. 2004 January; 147(1): E3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14691441

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Rapidly fatal acute amiodarone hepatitis occurring in the context of multiple organ failure. Author(s): MacFadyen RJ, Palmer TJ, Hisamuddin K. Source: International Journal of Cardiology. 2003 October; 91(2-3): 245-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559139

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Refractory amiodarone-associated thyrotoxicosis: an indication for thyroidectomy. Author(s): Claxton S, Sinha SN, Donovan S, Greenaway TM, Hoffman L, Loughhead M, Burgess JR. Source: The Australian and New Zealand Journal of Surgery. 2000 March; 70(3): 174-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765898

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Relations between monophasic action potential duration and refractoriness after cardioversion of persistent atrial fibrillation: results in wash-out and amiodaronetreated patients. Author(s): Pandozi C, Gentilucci G, Calo L, Castro A, Lamberti F, Loricchio ML, Santini L, Magris B, Bulava A, Peichl P, Santini M. Source: Ital Heart J. 2003 April; 4(4): 257-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784779

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Retinal evaluation of patients on chronic amiodarone therapy. Author(s): Shaikh S, Shaikh N, Chun SH, Spin JM, Blumenkranz MS, Marmor MF. Source: Retina (Philadelphia, Pa.). 2003 June; 23(3): 354-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824836

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Role of amiodarone in reducing atrial fibrillation after cardiac surgery in adults. Author(s): Haan CK, Geraci SA. Source: The Annals of Thoracic Surgery. 2002 May; 73(5): 1665-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022585

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Role of amiodarone in the era of the implantable cardioverter defibrillator. Author(s): Dorian P, Mangat I. Source: Journal of Cardiovascular Electrophysiology. 2003 September; 14(9 Suppl): S7881. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950525

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Role of amiodarone in the treatment of fetal supraventricular tachyarrhythmias and hydrops fetalis. Author(s): Khositseth A, Ramin KD, O'Leary PW, Porter CJ. Source: Pediatric Cardiology. 2003 September-October; 24(5): 454-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627312

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Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. Author(s): Naganuma M, Shiga T, Nishikata K, Tsuchiya T, Kasanuki H, Fujii E. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2001 October; 6(4): 363-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907638

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Severe cholestatic jaundice in the elderly induced by low-dose amiodarone. Author(s): Assy N, Khair G, Schlesinger S, Hussein O. Source: Digestive Diseases and Sciences. 2004 March; 49(3): 450-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15139496

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Shocks from pacemaker cardioverter defibrillators increase with amiodarone in patients at high risk for sudden cardiac death. Author(s): Shinde AA, Juneman EB, Mitchell B, Pierce MK, Gaballa MA, Goldman S, Thai H. Source: Cardiology. 2003; 100(3): 143-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631135

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SP-D as a marker of amiodarone-induced pulmonary toxicity. Author(s): Umetani K, Abe M, Kawabata K, Iida T, Kohno I, Sawanobori T, Kugiyama K. Source: Intern Med. 2002 September; 41(9): 709-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12322797

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Successful treatment of amiodarone-induced thyrotoxicosis. Author(s): Osman F, Franklyn JA, Sheppard MC, Gammage MD. Source: Circulation. 2002 March 19; 105(11): 1275-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11901034

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Supraventricular tachyarrythmia prophylaxis after coronary artery surgery in chronic obstructive pulmonary disease patients (early amiodarone prophylaxis trial). Author(s): Kuralay E, Cingoz F, Kilic S, Bolcal C, Gunay C, Demirkilic U, Tatar H. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2004 February; 25(2): 224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747117

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Surgery and anaesthesia for amiodarone-associated thyrotoxicosis. Author(s): Gough I, Meyer-Witting M. Source: The Australian and New Zealand Journal of Surgery. 2000 March; 70(3): 155-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765894

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Surgical management of amiodarone-associated thyrotoxicosis. Author(s): Gough IR, Gough J. Source: The Medical Journal of Australia. 2002 February 4; 176(3): 128-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936310

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Surgical management of amiodarone-induced thyrotoxicosis. Author(s): Franzese CB, Fan CY, Stack BC Jr. Source: Otolaryngology and Head and Neck Surgery. 2003 November; 129(5): 565-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595280

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Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by amiodarone: a report on two cases. Author(s): Ikegami H, Shiga T, Tsushima T, Nirei T, Kasanuki H. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2002 January; 7(1): 25-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000975

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Syndrome of inappropriate antidiuretic hormone-induced hyponatremia associated with amiodarone. Author(s): Patel GP, Kasiar JB. Source: Pharmacotherapy. 2002 May; 22(5): 649-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12013366

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Technetium-99m-DTPA aerosol scintigraphy in amiodarone induced pulmonary toxicity in comparison with Ga-67 scintigraphy. Author(s): Dirlik A, Erinc R, Ozcan Z, Atasever A, Bacakoglu F, Nalbantgil S, Ozhan M, Burak Z. Source: Ann Nucl Med. 2002 November; 16(7): 477-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508838

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The mysterious case of the lost pituitary: amiodarone-induced hypothyroidism. Author(s): Weston SN, Weston CF. Source: Hosp Med. 2000 January; 61(1): 64-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10735160

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The quest for an aqueous amiodarone. Author(s): Somberg JC, Molnar J. Source: American Journal of Therapeutics. 2003 November-December; 10(6): 458-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624286

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The role of amiodarone in the management of patients with cardiac arrest. Author(s): Franks AM, Watterson KS. Source: J Ark Med Soc. 2000 December; 97(6): 196-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12876823

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Three cases of severe acute hepatitis after parenteral administration of amiodarone: the active ingredient is not the only agent responsible for hepatotoxicity. Author(s): Giannattasio F, Salvio A, Varriale M, Picciotto FP, Di Costanzo GG, Visconti M. Source: Ann Ital Med Int. 2002 July-September; 17(3): 180-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12402666

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Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis. Author(s): Bogazzi F, Martino E, Dell'Unto E, Brogioni S, Cosci C, Aghini-Lombardi F, Ceccarelli C, Pinchera A, Bartalena L, Braverman LE. Source: J Endocrinol Invest. 2003 July; 26(7): 635-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594114

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Thyroidectomy using local anesthesia in critically ill patients with amiodaroneinduced thyrotoxicosis: a review and description of the technique. Author(s): Williams M, Lo Gerfo P. Source: Thyroid : Official Journal of the American Thyroid Association. 2002 June; 12(6): 523-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12165117

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Torsades de pointes and QT prolongation due to a combination of loratadine and amiodarone. Author(s): Atar S, Freedberg NA, Antonelli D, Rosenfeld T. Source: Pacing and Clinical Electrophysiology : Pace. 2003 March; 26(3): 785-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698686

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Toxicity and amiodarone. Author(s): Topham C, Brierley J, Tomlinson H. Source: International Journal of Radiation Oncology, Biology, Physics. 1988 May; 14(5): 1056. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3360650

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Treatment of type II amiodarone-induced thyrotoxicosis by either iopanoic acid or glucocorticoids: a prospective, randomized study. Author(s): Bogazzi F, Bartalena L, Cosci C, Brogioni S, Dell'Unto E, Grasso L, AghiniLombardi F, Rossi G, Pinchera A, Braverman LE, Martino E. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 May; 88(5): 19992002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727944

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Ultrastructural evidence of thyroid damage in amiodarone-induced thyrotoxicosis. Author(s): Cappiello E, Boldorini R, Tosoni A, Piraneo S, Bernasconi R, Raggi U. Source: J Endocrinol Invest. 1995 December; 18(11): 862-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8778159

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Unexplained bone marrow granulomas: is amiodarone the culprit? A report of 2 cases. Author(s): Mukhopadhyay S, Mukhopadhyay S, Abraham NZ Jr, Jones LA, Howard L, Gajra A. Source: American Journal of Hematology. 2004 February; 75(2): 110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755379

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Unusual interference from primary collection tube in a high-performance liquid chromatography assay of amiodarone. Author(s): Murthy VV. Source: Journal of Clinical Laboratory Analysis. 1997; 11(4): 232-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9219066

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Use dependence of amiodarone during the sinus tachycardia of exercise in coronary artery disease. Author(s): Cascio WE, Woelfel A, Knisley SB, Buchanan JW Jr, Foster JR, Gettes LS. Source: The American Journal of Cardiology. 1988 May 1; 61(13): 1042-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3364359

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Use of amiodarone in the postmyocardial infarction patient. Author(s): Ozdil E, Carlson TA, Massumi A. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 1995; 22(1): 40-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7787469

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Use of intravenous amiodarone for postoperative junctional ectopic tachycardia in children. Author(s): Laird WP, Snyder CS, Kertesz NJ, Friedman RA, Miller D, Fenrich AL. Source: Pediatric Cardiology. 2003 March-April; 24(2): 133-7. Epub 2002 October 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370794

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Use of oral cholecystographic agents in the treatment of amiodarone-induced hyperthyroidism. Author(s): Chopra IJ, Baber K. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 October; 86(10): 4707-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600529

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Use of population modeling to define rational monitoring of amiodarone hepatic effects. Author(s): Pollak PT, Shafer SL. Source: Clinical Pharmacology and Therapeutics. 2004 April; 75(4): 342-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15060512

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Use, value, and toxicity of amiodarone. Author(s): Rothenberg F, Franklin JO, DeMaio SJ. Source: Heart Dis Stroke. 1994 January-February; 3(1): 19-23. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8137059

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Usefulness of Holter monitoring in predicting efficacy of amiodarone therapy for sustained ventricular tachycardia associated with coronary artery disease. Author(s): Nasir N Jr, Doyle TK, Wheeler SH, Pacifico A. Source: The American Journal of Cardiology. 1994 March 15; 73(8): 554-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7511872

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Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. Author(s): Funck-Brentano C, Becquemont L, Kroemer HK, Buhl K, Knebel NG, Eichelbaum M, Jaillon P. Source: Clinical Pharmacology and Therapeutics. 1994 March; 55(3): 256-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8143391

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Vasculitis associated with amiodarone treatment. Author(s): Gutierrez R, Del Pozo J, Carrion C, De Lucas R, Garcia B, Casado M, Jimenez E. Source: The Annals of Pharmacotherapy. 1994 April; 28(4): 537. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8038483

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Ventricular arrhythmias--update on the use of amiodarone. Author(s): Kerin NZ. Source: Journal of Clinical Pharmacology. 1989 May; 29(5): 386. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2738175

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Ventricular fibrillation after intravenous amiodarone in Wolff-Parkinson-White syndrome with atrial fibrillation. Author(s): Boriani G, Biffi M, Frabetti L, Azzolini U, Sabbatani P, Bronzetti G, Capucci A, Magnani B. Source: American Heart Journal. 1996 June; 131(6): 1214-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8644602

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Ventricular fibrillation in two infants treated with amiodarone hydrochloride. Author(s): Pohlgeers A, Villafane J. Source: Pediatric Cardiology. 1995 March-April; 16(2): 82-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7784241

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Very early onset of acute amiodarone pulmonary toxicity presenting with hemoptysis. Author(s): Goldstein I, Topilsky M, Segev D, Isakov A, Heller I. Source: Chest. 1997 May; 111(5): 1446-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9149610

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Visual changes secondary to initiation of amiodarone: a case report and review involving ocular management in cardiac polypharmacy. Author(s): Castells DD, Teitelbaum BA, Tresley DJ. Source: Optometry. 2002 February; 73(2): 113-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12365708

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Visual compatibility of amiodarone hydrochloride injection with various intravenous drugs. Author(s): Chalmers JR, Bobek MB, Militello MA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 March 15; 58(6): 504-6. Erratum In: Am J Health Syst Pharm.2003 June 1; 60(11): 1095-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11286148

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Visual functions and adverse ocular effects in patients with amiodarone medication. Author(s): Ikaheimo K, Kettunen R, Mantyjarvi M. Source: Acta Ophthalmologica Scandinavica. 2002 February; 80(1): 59-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11906306

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Vitamin E reduces accumulation of amiodarone and desethylamiodarone and inhibits phospholipidosis in cultured human cells. Author(s): Honegger UE, Scuntaro I, Wiesmann UN. Source: Biochemical Pharmacology. 1995 June 16; 49(12): 1741-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7598736

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What internists should know about amiodarone. Author(s): Murphy MT, Wilkoff BL. Source: Cleve Clin J Med. 1998 March; 65(3): 159-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9540249

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Worsening of ventricular tachycardia by amiodarone. Author(s): Gallastegui JL, Bauman JL, Anderson JL, Winkle RA, Ezri MD, Westveer DC, Swiryn S. Source: Journal of Clinical Pharmacology. 1988 May; 28(5): 406-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3392238

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CHAPTER 2. NUTRITION AND AMIODARONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and amiodarone.

Finding Nutrition Studies on Amiodarone The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “amiodarone” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “amiodarone” (or a synonym): •

24 h-kinetics of iodide uptake in amiodarone induced hypothyroidism. Author(s): Department of Endocrinology, Erasme Hospital, Brussels, Belgium. Source: Unger, J Surmont, D W Sarot, J Soupart, A Dumont, J E Thyroidology. 1989 August; 1(2): 101-2

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A comparative analysis of the loss of amiodarone from small and large volume PVC and non-PVC infusion systems. Author(s): Repatriation General Hospital, Daw Park, South Australia. Source: Peters, P G Hayball, P J Anaesth-Intensive-Care. 1990 May; 18(2): 241-5 0310057X

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A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer. Author(s): National Institutes of Health, Bethesda, MD 20892. Source: Bates, S E Meadows, B Goldspiel, B R Denicoff, A Le, T B Tucker, E Steinberg, S M Elwood, L J Cancer-Chemother-Pharmacol. 1995; 35(6): 457-63 0344-5704

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Acute and chronic effects of amiodarone on mammalian ventricular cells. Author(s): Department of Circulation, Nagoya University, Japan. Source: Kodama, I Kamiya, K Honjo, H Toyama, J Jpn-Heart-J. 1996 September; 37(5): 719-30 0021-4868

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Compared efficacy of quinidine, amiodarone and diltiazem on both nomotopic and ectopic automaticity in the rat heart. Source: Gonzalez Sicilia, L Laorden, M L Villalobos, J P Perez, D Hernandez, J MethodsFind-Exp-Clin-Pharmacol. 1987 January; 9(1): 19-22 0379-0355

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Comparison of the effects of amiodarone and ipodate on the rat heart. Author(s): Department of Medicine, Wayne State University, Detroit, Michigan. Source: Bagchi, N Brown, T R Banerjee, S K Horm-Metab-Res. 1989 April; 21(4): 182-4 0018-5043

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Disruption of mitochondrial function and cellular ATP levels by amiodarone and Ndesethylamiodarone in initiation of amiodarone-induced pulmonary cytotoxicity. Author(s): Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada. Source: Bolt, M W Card, J W Racz, W J Brien, J F Massey, T E J-Pharmacol-Exp-Ther. 2001 September; 298(3): 1280-9 0022-3565

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Effect of amiodarone and sotalol on the defibrillation threshold in comparison to patients without antiarrhythmic drug treatment. Author(s): Medical Department III, University of Tubingen, Germany. [email protected] Source: Kuhlkamp, V Mewis, C Suchalla, R Mermi, J Dornberger, V Seipel, L Int-JCardiol. 1999 June 1; 69(3): 271-9 0167-5273

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Effects of amiodarone on thyroid hormone-responsive gene expression in rat liver. Author(s): Department of Endocrinology, University of Amsterdam, The Netherlands. Source: Hartong, R Wiersinga, W M Lamers, W H Plomp, T A Broenink, M van Beeren, M H Horm-Metab-Res-Suppl. 1987; 1734-43 0170-5903

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Effects of vitamin E on cytotoxicity of amiodarone and N-desethylamiodarone in isolated hamster lung cells. Author(s): Department of Pharmacology and Toxicology, Botterell Hall Room 535, Queen's University, Ont., K7L 3N6, Kingston, Canada.

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Source: Bolt, M W Racz, W J Brien, J F Massey, T E Toxicology. 2001 September 25; 166(3): 109-18 0300-483X •

Hemodynamic and electrocardiographic effects of graded doses of amiodarone in healthy dogs anesthetized with morphine/alpha chloralose. Author(s): Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus 43210-1092, USA. Source: Bicer, S Schwartz, D S Nakayama, T Hamlin, R L J-Vet-Intern-Med. 2000 JanFebruary; 14(1): 90-5 0891-6640

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Identification of a novel, inhibitory action of amiodarone on vesicular monoamine transport. Author(s): Molecular Neurocardiology Laboratory, Baker Medical Research Institute, Prahan, Victoria, Australia. Source: Haikerwal, D Dart, A M Little, P J Kaye, D M J-Pharmacol-Exp-Ther. 1999 February; 288(2): 834-7 0022-3565

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Long-term prevention of atrial fibrillation after coronary artery bypass surgery: comparison of quinidine, verapamil, and amiodarone in maintaining sinus rhythm. Author(s): Department of Cardiovascular Surgery, Gulhane Military Medical Academy, Ankara, Turkey. Source: Yilmaz, A T Demirkilic, U Arslan, M Kurulay, E Ozal, E Tatar, H Ozturk, O JCard-Surg. 1996 Jan-February; 11(1): 61-4 0886-0440

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Metabolism of amiodarone (part I): identification of a new hydroxylated metabolite of amiodarone. Author(s): Cardiovascular Therapy Research Unit, Department of Internal Medicine, University Hospital of Zurich, Ramistrasse 100, CH-8091 Zurich, Switzerland. [email protected] Source: Ha, H R Bigler, L Binder, M Kozlik, P Stieger, B Hesse, M Altorfer, H R Follath, F Drug-Metab-Dispos. 2001 February; 29(2): 152-8 0090-9556

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Oral amiodarone increases the efficacy of direct-current cardioversion in restoration of sinus rhythm in patients with chronic atrial fibrillation. Author(s): Cardiology Department, Piacenza General Hospital, Piacenza, Italy. Source: Capucci, A Villani, G Q Aschieri, D Rosi, A Piepoli, M F Eur-Heart-J. 2000 January; 21(1): 66-73 0195-668X

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Refractory vasodilation after cardiopulmonary bypass for heart transplantation in recipients on combined amiodarone and angiotensin-converting enzyme inhibitor therapy: a role for vasopressin administration. Author(s): Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA. Source: Mets, B Michler, R E Delphin, E D Oz, M C Landry, D W J-Cardiothorac-VascAnesth. 1998 June; 12(3): 326-9 1053-0770

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Silymarin and vitamin E do not attenuate and vitamin E might even enhance the antiarrhythmic activity of amiodarone in a rat reperfusion arrhythmia model. Author(s): EGIS Pharmaceuticals Ltd, Budapest, Hungary. Source: Gyonos, I Agoston, M Kovacs, A Szenasi, G Vereckei, A Cardiovasc-Drugs-Ther. 2001; 15(3): 233-40 0920-3206

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Slowing of the inactivation of cardiac voltage-dependent sodium channels by the amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015). Author(s): Centre for Experimental Surgery and Anaesthesiology, University of Leuven, Leuven, Belgium.

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Source: Macianskiene, R Viappiani, S Sipido, K R Mubagwa, K J-Pharmacol-Exp-Ther. 2003 January; 304(1): 130-8 0022-3565 •

The incidence and clinical significance of amiodarone and acenocoumarol interaction. Author(s): Department of Medicine B, Hadassah University Hospital, Jerusalem, Israel. Source: Caraco, Y Chajek Shaul, T Thromb-Haemost. 1989 November 24; 62(3): 906-8 0340-6245

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Toxicity of amiodarone and amiodarone analogues on isolated rat liver mitochondria. Author(s): Division of Clinical Pharmacology and Toxicology, University Hospital of Basel, Petersgraben 4, CH-4031, Basel, Switzerland Source: Spaniol, M Bracher, R Ha, H R Follath, F Krahenbuhl, S J-Hepatol. 2001 November; 35(5): 628-36 0168-8278

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Transient fetal hypothyroidism due to direct fetal administration of amiodarone for drug resistant fetal tachycardia. Author(s): Academisch Ziekenhuis Kinderen, Vrije Universiteit Brussel, Brussels-Jette, Belgium. Source: Vanbesien, J Casteels, A Bougatef, A De Catte, L Foulon, W De Bock, S Smitz, J De Schepper, J Am-J-Perinatol. 2001; 18(2): 113-6 0735-1631

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Nutrition

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to amiodarone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND AMIODARONE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to amiodarone. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to amiodarone and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “amiodarone” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to amiodarone: •

A brief history of sudden cardiac death and its therapy. Author(s): Janse MJ. Source: Pharmacology & Therapeutics. 2003 October; 100(1): 89-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550507

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A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer. Author(s): Bates SE, Meadows B, Goldspiel BR, Denicoff A, Le TB, Tucker E, Steinberg SM, Elwood LJ. Source: Cancer Chemotherapy and Pharmacology. 1995; 35(6): 457-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7882454

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Acute antiarrhythmic effects of intravenously administered amiodarone on canine ventricular arrhythmia. Author(s): Awaji T, Wu ZJ, Hashimoto K.

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Source: Journal of Cardiovascular Pharmacology. 1995 December; 26(6): 869-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8606522 •

Amiodarone and amiodarone plus digitalis in the treatment of paroxismal supraventricular reciprocating tachyarrhythmias. Author(s): Furlanello F, Inama G, Ferrari M, Padrini R, Piovan D, Guarnerio M, Vergara G, Del Favero A, Dal Forno P, Disertori M. Source: Pharmacol Res Commun. 1982 September; 14(8): 731-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7146058

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Amiodarone in long term prophylaxis. Author(s): Katritsis D, Camm AJ. Source: Drugs. 1991; 41 Suppl 2: 54-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1711969

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Amiodarone N-deethylation by CYP2C8 and its variants, CYP2C8*3 and CYP2C8 P404A. Author(s): Soyama A, Hanioka N, Saito Y, Murayama N, Ando M, Ozawa S, Sawada J. Source: Pharmacology & Toxicology. 2002 October; 91(4): 174-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12530467

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Amiodarone, nifedipine, sodium cromoglycate. Author(s): Hollman A. Source: British Heart Journal. 1991 January; 65(1): 57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1899585

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Anti-arrhythmic action of cycloprotobuxine-A. Author(s): Wang YX, Liu JW, Tan YH, Sheng BH. Source: Zhongguo Yao Li Xue Bao. 1989 September; 10(5): 389-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2618724

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Cardiac arrhythmias during experimental induction and management of myocardial infarction in the dog. Author(s): Beyer M, Hoffer H, Eggeling T, Mierdl S, Beyer U, Hannekum A. Source: J Exp Anim Sci. 1992 August; 35(2): 89-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1390961

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Cellular protection with proanthocyanidins derived from grape seeds. Author(s): Bagchi D, Bagchi M, Stohs S, Ray SD, Sen CK, Preuss HG. Source: Annals of the New York Academy of Sciences. 2002 May; 957: 260-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074978

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Combined amiodarone and silymarin treatment, but not amiodarone alone, prevents sustained atrial flutter in dogs. Author(s): Vereckei A, Zipes DP, Besch H Jr. Source: Journal of Cardiovascular Electrophysiology. 2003 August; 14(8): 861-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890050

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Competitive, non-competitive and cooperative interactions between substrates of Pglycoprotein as measured by its ATPase activity. Author(s): Litman T, Zeuthen T, Skovsgaard T, Stein WD. Source: Biochimica Et Biophysica Acta. 1997 August 22; 1361(2): 169-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9300798

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Decreased transport of thyroxine (T4), 3,3',5-triiodothyronine (T3) and 3,3',5'triiodothyronine (rT3) into rat hepatocytes in primary culture due to a decrease of cellular ATP content and various drugs. Author(s): Krenning EP, Docter R, Bernard B, Visser T, Hennemann G. Source: Febs Letters. 1982 April 19; 140(2): 229-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7084465

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Effect of amiodarone on release of cytokines from mouse alveolar macrophages pretreated with eicosapentaenoic acid. Author(s): Futamura Y. Source: Japanese Journal of Pharmacology. 1995 December; 69(4): 335-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8786636

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Effects of amiodarone, cyclosporin A, and PSC 833 on the cytotoxicity of mitoxantrone, doxorubicin, and vincristine in non-P-glycoprotein human small cell lung cancer cell lines. Author(s): van der Graaf WT, de Vries EG, Timmer-Bosscha H, Meersma GJ, Mesander G, Vellenga E, Mulder NH. Source: Cancer Research. 1994 October 15; 54(20): 5368-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7923167

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Effects of congestive heart failure on the pharmacokinetics and pharmacodynamics of antiarrhythmic agents. Author(s): Woosley RL, Echt DS, Roden DM. Source: The American Journal of Cardiology. 1986 January 31; 57(3): 25B-33B. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3080860

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Effects of dietary vitamin E supplementation on pulmonary morphology and collagen deposition in amiodarone- and vehicle-treated hamsters. Author(s): Card JW, Leeder RG, Racz WJ, Brien JF, Bray TM, Massey TE.

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Source: Toxicology. 1999 April 15; 133(2-3): 75-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10378474 •

Effects of Panax notoginseng saponin Rg1 on cardiac electrophysiological properties and ventricular fibrillation threshold in dogs. Author(s): Wu W, Zhang XM, Liu PM, Li JM, Wang JF. Source: Zhongguo Yao Li Xue Bao. 1995 September; 16(5): 459-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8701769

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Erythrocyte adenosine transport. A rapid screening test for cardiovascular drugs. Author(s): Yeung PK, Mosher SJ, Li R, Farmer PS, Klassen GA, Pollak PT, McMullen M, Ferrier G. Source: Journal of Pharmacological and Toxicological Methods. 1993 November; 30(3): 163-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8305718

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FK-506 (fujimycin) reverses the multidrug resistance of tumor cells in vitro. Author(s): Pourtier-Manzanedo A, Boesch D, Loor F. Source: Anti-Cancer Drugs. 1991 June; 2(3): 279-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1724925

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Formation of an inactive cytochrome P-450Fe(II)-metabolite complex after administration of amiodarone in rats, mice and hamsters. Author(s): Larrey D, Tinel M, Letteron P, Geneve J, Descatoire V, Pessayre D. Source: Biochemical Pharmacology. 1986 July 1; 35(13): 2213-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3729976

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Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Author(s): Miller LG. Source: Archives of Internal Medicine. 1998 November 9; 158(20): 2200-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9818800

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High dose oral amiodarone added to doxorubicin and vindesine for overcoming multidrug resistance in solid tumors. Author(s): van der Graaf WT, Buter J, de Vries EG, Willemse PH, Sleijfer DT, Mulder NH. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1994 September; 5(7): 659-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7993847

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•

Implantable defibrillators and/or amiodarone: alternatives or complementary therapies. Author(s): Dorian P, Newman D, Greene M. Source: Int J Clin Pract. 1998 September; 52(6): 425-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9894382

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In vitro and in vivo modulation of multi-drug resistance with amiodarone. Author(s): van der Graaf WT, de Vries EG, Uges DR, Nanninga AG, Meijer C, Vellenga E, Mulder PO, Mulder NH. Source: International Journal of Cancer. Journal International Du Cancer. 1991 June 19; 48(4): 616-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1646180

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In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract. Author(s): Ray SD, Patel D, Wong V, Bagchi D. Source: Res Commun Mol Pathol Pharmacol. 2000; 107(1-2): 137-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11334364

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Iodine-induced subclinical hypothyroidism in euthyroid subjects with a previous episode of amiodarone-induced thyrotoxicosis. Author(s): Roti E, Minelli R, Gardini E, Bianconi L, Gavaruzzi G, Ugolotti G, Neri TM, Braverman LE. Source: The Journal of Clinical Endocrinology and Metabolism. 1992 November; 75(5): 1273-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1331165

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Protective effects of curcumin against amiodarone-induced pulmonary fibrosis in rats. Author(s): Punithavathi D, Venkatesan N, Babu M. Source: British Journal of Pharmacology. 2003 August; 139(7): 1342-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890714

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Silymarin and vitamin E do not attenuate and vitamin E might even enhance the antiarrhythmic activity of amiodarone in a rat reperfusion arrhythmia model. Author(s): Gyonos I, Agoston M, Kovacs A, Szenasi G, Vereckei A. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2001; 15(3): 233-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11713891

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Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats.

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Author(s): Agoston M, Orsi F, Feher E, Hagymasi K, Orosz Z, Blazovics A, Feher J, Vereckei A. Source: Toxicology. 2003 August 28; 190(3): 231-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927377 •

The effect of amiodarone and/or antioxidant treatment on splenocyte blast transformation. Author(s): Agoston M, Cabello RG, Blazovics A, Feher J, Vereckei A. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 January; 303(1-2): 87-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11163028

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Toxicity of amiodarone on mouse pulmonary endothelial cells cultured with or without alveolar macrophages. Author(s): Futamura Y. Source: J Toxicol Sci. 1996 November; 21(4): 253-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8959650

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

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The following is a specific Web list relating to amiodarone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Hypothyroidism Source: Healthnotes, Inc.; www.healthnotes.com Photosensitivity Source: Healthnotes, Inc.; www.healthnotes.com

•

Herbs and Supplements Amiodarone Source: Healthnotes, Inc.; www.healthnotes.com Amiodarone Alternative names: Cordarone, Pacerone Source: Prima Communications, Inc.www.personalhealthzone.com Echinacea Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. PATENTS ON AMIODARONE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “amiodarone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on amiodarone, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Amiodarone By performing a patent search focusing on amiodarone, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on amiodarone: •

Amiodarone as an antifungal agent Inventor(s): Courchesne; William E. (Soda Springs, CA) Assignee(s): University and College of Nevada, Reno (Reno, NV) Patent Number: 6,221,903 Date filed: January 10, 2000 Abstract: The present invention relates to methods of treating fungal infections and methods of killing or inhibiting growth of fungi with an amiodarone compound. Excerpt(s): The present invention relates generally to methods of treating fungal infections and methods of killing or inhibiting growth of fungi with an amiodarone compound. Pathogenic fungi occur world wide and are major agricultural and health pests. Fungal infections in humans range from superficial and cutaneous to deeply invasive and disseminated. Treatment of fungal infections has lagged behind bacterial chemotherapy. There are substantially fewer antifungal drugs than antibacterial drugs. In the last two decades, nearly 12 million people have died of acquired immunodeficiency syndrome (AIDS) after being infected with HIV, the humanimmunodeficiency virus. AIDS is defined by the occurence of at least one of more than two dozen opportunistic infections. Fungal opportunistic infections such as candidiasis, cryptococcosis, and histoplasmosis, occur frequently in patients with AIDS. Among the opportunistic infections, fungal infections caused by Pneumocystis, Candida, Cryptococcus, or Histoplasma were the first to occur in more than 50% of persons with AIDS; and at time of death, nearly 85% of decedents had a fungal infection (Jones, et al., 1999, MMWR 48: 1-22). Web site: http://www.delphion.com/details?pn=US06221903__

•

Amiodarone-containing parenteral administration Inventor(s): Doty; Mark J. (Grayslake, IL), Eilert; Jan Y. (Wauconda, IL), Kipp; James E. (Wauconda, IL), Rebbeck; Christine L. (Algonquin, IL) Assignee(s): Baxter International (Deerfield, IL) Patent Number: 6,479,541 Date filed: March 30, 2000 Abstract: The present invention provides an amiodarone parenteral solution suitable for intravenous administration without the necessity of dilution. The parenteral solution has an amiodarone concentration from 0.2 to 10 mg/ml and a buffer solution selected from the group consisting of lactate buffer, methanesulfonate buffer, or combinations thereof, the solution having a pH within the range from approximately 2.5-4.5. Excerpt(s): The present invention relates to an amiodarone antiarrhythmic agent and more particularly to a parenteral solution of amiodarone for intravenous infusion. Amiodarone is a type III antiarrhythmic agent that exhibits a broad spectrum of activity. The hydrochloride salt is currently marketed in ampoules suitable for intravenous administration following dilution in dextrose (Cordarone IV, Wyeth-Ayrest). The pH range of the diluted product (measured in the lab) is from 3.8-4.0. Amiodarone free base

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has an extremely low estimated intrinsic solubility in water (18 6 ng/mL). The free base is neutral and by protonation with acid is converted to a more water-soluble trialkylammonium ion. However, the hydrochloride salt (used in the current commercial product) is not appreciably soluble in water at moderately low pH (3.8-4.5). Therefore, the commercial formulation contains polysorbate 80 as a surfactant to aid in dissolving and solubilizing the drug. This may be a serious drawback because glycol ethers and their derivatives such as polyethylene glycols (PEGs) or polysorbates (Tweens) are known to contribute to pain on injection, and may also induce anaphylactic reactions. Tween 80 has also been associated with cardiodepression, causing hypotension (Gough et al., "Hypotensive Action of Commercial Intravenous Amiodarone and Polysorbate 80 in Dogs," Journal of Cardiovascular Pharmacology, 1982, 375-380). Web site: http://www.delphion.com/details?pn=US06479541__ •

Compounds for treatment of cardiac arrhythmia synthesis, and methods of use Inventor(s): Druzgala; Pascal (Santa Rosa, CA), Milner; Peter G. (Los Altos Hills, CA) Assignee(s): Aryx Therapeutics (Los Altos Hill, CA) Patent Number: 6,316,487 Date filed: October 6, 2000 Abstract: The subject invention pertains to novel compounds, and compositions comprising the compounds, for the treatment of cardiac arrhythmias. The subject invention further concerns a method of making the novel compounds. The novel compounds are rapidly metabolized analogs of amiodarone, having the distinct and advantageous characteristic of being metabolized to a less lipophilic compound. The new compounds can have particular utility for treating life-threatening ventricular tachyarrhythmias, especially in patients with congestive heart failure (CHF). The product can also provide effective management for ventricular arrhythmias and supraventricular arrhythmias, including atrial fibrillation and re-entrant tachyarrhythmias involving accessory pathways. Excerpt(s): Congestive heart failure (CHF) is a disease affecting approximately 2% of the population of the United States (Sami, M. H. [1991] J. Clin. Pharmacol. 31:1081). Despite advances in the diagnosis and treatment of CHF, the prognosis remains poor with a 5year mortality rate higher than 50% from the time of diagnosis (McFate Smith, W. [1985] Am. J. Cardiol. 55:3A; McKee, P. A., W. P. Castelli, P. M. McNamara, W. B. Kannel [1971] N. Engl. J. Med. 285:1441). In patients with CHF, the rate of survival is lowest in those patients with severe depression of left ventricular function and patients who have frequent ventricular arrhythmias. Patients with ventricular arrhythmias and ischemic cardiomyopathy have an increased risk of sudden death. The presence of ventricular tachycardia in patients with severe CHF results in a three-fold increase in sudden death compared to those without tachycardia (Bigger, J. T., Jr. [1987] Circulation 75(suppl.IV):28). Because of the high prevalence of sudden unexpected death in patients with CHF, there has been a growing interest in the prognostic significance of arrhythmias in these patients. Several compounds have been used in the management of cardiac arrhythmias in patients with congestive heart failure. Unfortunately, antiarrhythmic drug therapy has been disappointing. The efficacy of antiarrhythmic drugs markedly decreases as left ventricular function declines, such that only a small fraction of patients with CHF are responsive to antiarrhythmic therapy. No antiarrhythmic drug has prevented sudden death in patients with CHF. There is even a

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question of increased mortality associated with certain antiarrhythmic drugs (the CAST investigators [1989] N. Engl. J. Med. 321:406). Scientists define tachycardia and ventricular fibrillation as being of multiple nature. It now seems clear, and is accepted in the art, that re-entry is the underlying mechanism to most sustained arrhythmias. Prolonging ventricular repolarization as a means of preventing ventricular arrhythmias has consequently received renewed attention. This points to Class-III agents as drugs of choice in the treatment of arrhythmias. A Class-III agent, as referred to herein, is an agent which is classified as such in the Vaughan-Williams classification of antiarrhythmic drugs. A Class-III agent exerts its primary antiarrhythmic activity by prolonging cardiac action potential duration (APD), and thereby the effective refractory period (ERP), with no effect on conduction. These electrophysiological changes, which are brought about by blockade of cardiac potassium channels, are well known in the art. Because the blockade of cardiac potassium channels is not associated with depression of the contractile function of the heart, Class-III agents are particularly attractive for use in patients with CHF. Unfortunately, the existing Class-III agents are limited in their utility by additional pharmacological activities, lack of good oral bioavailability, or a poor toxicity profile. The only two Class III agents currently marketed are bretylium (i.v. only) and amiodarone (i.v. and p.o.). Web site: http://www.delphion.com/details?pn=US06316487__ •

Methods for treating arrhythmia using acetate buffer solutions of amiodarone Inventor(s): Somberg; John C. (Lake Forest, IL) Assignee(s): Academic Pharmaceuticals, LP (Lake Bluff, IL) Patent Number: 6,030,998 Date filed: July 9, 1999 Abstract: Disclosed herein are methods for treating human patients suffering from arrhythmia comprising administration to the human a solutions containing a 3diethylaminoethoxybenzoyl-benzofuran in acetate buffer. Excerpt(s): The present invention relates to the use of parenteral solutions containing 3diethylaminoethoxybenzoylbenzofurans in the treatment of arrhythmia. More specifically, the present invention relates to the use of a parenteral solution of 2-n-butyl3-(3,5-diiodo-4-(.beta.-N-diethylaminoethoxy)benzoyl)benzofuran in the treatment of arrhythmia. 2-n-butyl-3-(3,5-diiodo-4-(.beta.-N-diethylaminoethoxy)benzoyl) benzofuran [4-(2-(diethyl-amino)ethoxy)-3,5-diiodophenyl 2-butylbenzo[b]furan-3-yl ketone] (hereinafter amiodarone) has been approved in an oral tablet form (CORDARONE.RTM.) for the treatment of life-threatening ventricular tachyarrhythmias in the United States since 1985. This drug is useful not only in treating these arrhythmias but also in treating less severe ventricular arrhythmias and many supraventricular arrhythmias including atrial fibrillation and reentrant tachyarrhythmias involving accessory pathways. To treat arrhythmias, the compound may be administered in oral dosage forms such as in the form of a 200 mg tablet, or it may be administered in the form of an intravenous solution. See, for example, Escoubet, B. et al., "Suppression of Arrhythmias Within Hours After Single Oral Dose of Amiodarone and Relation to Plasma and Myocardial Concentrations", Am. J. Cardiol., (1985), 55:696-702, Mostow et al., "Rapid Suppression of Complex Ventricular Arrhythmias With High-Dose Oral Amiodarone", Circulation, (1986), 73:1231-8, Morady et al., "Intravenous Amiodarone in the Acute Treatment of Recurrent Symptomatic Ventricular Tachycardia", Am. J. Cardiol., (1983), 51:156-9 and Kadish et al. "The Use of Intravenous Amiodarone in the

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Acute Therapy of Life-Threatening Tachyarrhythmias". Progress in Cardiovascular Diseases, (1989), 31:4, 281-294. Web site: http://www.delphion.com/details?pn=US06030998__ •

Parenteral solutions containing amiodarone in acetate buffer solution Inventor(s): Ehrenpreis; Seymour (Skokie, IL), Somberg; John C. (New Rochelle, NY) Assignee(s): Academic Pharmaceuticals, Inc. (Lake Forest, IL) Patent Number: 5,234,949 Date filed: April 1, 1992 Abstract: Disclosed herein are parenteral solutions containing 3diethylaminoethoxybenzoyl-benzofurans, such as amiodarone, in acetate buffer useful in the treatment of arrhythmias. Excerpt(s): Amiodarone has been approved in an oral tablet form (CORDARONE.RTM.) for the treatment of life-threatening ventricular tachyarrhythmias in the United States since 1985. This drug is useful not only in treating these arrhythmias but also in treating less severe ventricular arrhythmias and many supraventricular arrhythmias including atrial fibrillation and reentrant tachyarrhythmias involving accessory pathways. To treat arrhythmias, the compound may be administered in oral dosage forms such as in the form of a 200 mg tablet, or it may be administered in the form of an intravenous solution. Please see, for example, Escoubet, B. et al., "Suppression of Arrhythmias Within Hours After Single Oral Dose of Amiodarone and Relation to Plasma and Myocardial Concentrations", Am. J. Cardiol., (1985), 55:696-702, Mostow et al., "Rapid Suppression of Complex Ventricular Arrhythmias With High-Dose Oral Amiodarone", Circulation, (1986), 73:1231-8, Morady et al., "Intravenous Amiodarone in the Acute Treatment of Recurrent Symptomatic Ventricular Tachycardia", Am. J. Cardiol., (1983), 51:156-9 and Kadish et al. "The Use of Intravenous Amiodarone in the Acute Therapy of Life-Threatening Tachyarrhythmias". Progress in Cardiovascular Diseases, (1989), 31:4, 281-294. Amiodarone is practically insoluble or slightly soluble in an aqueous solvent. Hence, it is difficult to formulate a dosage form suitable for intravenous administration. To aid the dissolution in water, for example, a surfactant has been suggested. Thus, the prior art intravenous dosage form for this compound termed I.V. Cordarone, comprises amiodarone dissolved in a solvent comprising polysorbate 80 available under the tradename Tween-80, and benzyl alcohol. Prior art intravenous solutions of amiodarone will be designated IV Cordarone herein. Web site: http://www.delphion.com/details?pn=US05234949__

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Pharmaceutical amiodarone composition for parenteral delivery Inventor(s): Bellamy; Regine (Restinclieres, FR), Gautier; Jean-Claude (Clapiers, FR) Assignee(s): Sanofi (Paris, FR) Patent Number: 6,143,778 Date filed: March 13, 1998 Abstract: The invention relates to a pharmaceutical composition for parenteral administration, characterized in that it comprises:from 1.5 to 8% by weight of an active principle consisting of amiodarone or one of the pharmaceutically acceptable salts

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thereofa physiologically acceptable buffer solution capable of solubilizing the active principle and of maintaining the pH of the composition between 2.4 and 3.8a nonionic hydrophilic surfactant. Excerpt(s): The present invention relates generally to a novel pharmaceutical composition containing a substituted benzoylbenzofuran as active principle. In particular, the invention relates to a pharmaceutical composition for parenteral administration containing, as active principle, 2-n-butyl-3-[3,5-diiodo-4-(2diethylaminoethoxy)benzoyl]benzofuran, also known as amiodarone, or one of the pharmaceutically acceptable salts thereof, preferably its hydrochloride. This compound, known for its beneficial properties on the cardiovascular system, is currently widely used, in the form of its hydrochloride, as an antiarrhythmic agent and as an active principle in the fundamental treatment of coronary insufficiency. Web site: http://www.delphion.com/details?pn=US06143778__ •

Pharmaceutical tablet of amiodarone salt Inventor(s): Daisy, Jr.; Samuel (Minneapolis, MN), Tourek; William J. (Plymouth, MN) Assignee(s): Upsher-Smith Laboratories, Inc. (Minneapolis, MN) Patent Number: 5,785,995 Date filed: April 11, 1997 Abstract: An orally administered tablet comprising a therapeutic amount of a pharmaceutically acceptable salt of amiodarone (e.g., an acid salt of amiodarone such as amiodarone hydrochloride) is described. Other ingredients include a disaccharide which is preferably a reducing disaccharide, pregelatinized starch, and an alkali metal starch glycolate. The tablet preferably also comprises at least one of the following: a) 2 to 6% by weight stearic acid, b) less than 1% by weight magnesium stearate, c) 2 to 25% by weight of wet binder, and d) less than 0.1% by weight of silica gel. Excerpt(s): The present invention relates to oral dosing of pharmaceuticals and especially to the compacted tablet dosing of pharmaceutically acceptable salts of amiodarone, such as amiodarone hydrochloride. Pharmaceutically active ingredients are conveniently and commonly provided to patients in oral dosages. These dosages are commonly provided in powder, solution, tablet, and capsule forms, depending upon the properties of the active ingredient and medically recommended methods of ingestion to achieve optimum pharmacological effects, patient convenience, and patient acceptability. Tabletting is a particularly convenient method of providing medication to patients in an easily ingested and fast acting form, at least for those types of medication which can tolerate some degree of environmental (especially aerial) exposure, with or without protective coatings on the tablets. Tablets are generally formed by compaction and/or molding of the active ingredient and other materials generally useful for shaping, holding (binding), and releasing the materials when ingested. Tablets may comprise, for example, an active ingredient, a binder (e.g., pregelatinized starch), lubricant (e.g., stearic acid for facilitating molding), colloidal silica and/or silica gel to retain moisture compatibility, dyes, water softenable/soluble binders such as polyvinylpyrollidone (e.g., as sold under the trademark of "Povidone.TM." or "Kollidon.TM."), and the like. Web site: http://www.delphion.com/details?pn=US05785995__

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Synergistic compositions of amiodarone and beta blockers Inventor(s): Baligadoo; Soorianarain (Center of Research Medicales, SSR, Univerisity de Maurice, Moka, MU) Assignee(s): none reported Patent Number: 5,455,269 Date filed: October 8, 1993 Abstract: There are disclosed pharmaceutical preparations and methods for the use thereof which have a cardioprotective action useful in coronary insufficiency, in the prevention of the constitution of an infarction or of sudden death. It consists in the utilization of amiodarone and a beta-blocker at certain diodes and in certain ratios whereby the gravity test is enhanced. Excerpt(s): There are disclosed pharmaceutical preparations and methods for the use thereof which have a cardioprotective action useful in coronary insufficiency, in the prevention of the constitution of an infarction or of sudden death. These methods comprise the utilization of amiodarone, a nitrate derivative and a beta-blocker. In coronary insufficiency, one observes a high frequency of sudden death particularly in acute coronary insufficiency which may culminate in the occurrence of myocardial infarction. Some cases of sudden death are related to arrhythmias consecutive to coronary insufficiency Itself. It would be desirable to contemporaneously decrease the consumption of oxygen, increase the myocardial irrigation and also exercise a preventive effect against arrhythmias. It has been observed that coronary thrombosis induces a phenomenon called stunned myocardial syndrome consecutive to the prolonged ischaemia of the heart. This phenomenon prevents the obtention of optimal benefits following reperfusion. Web site: http://www.delphion.com/details?pn=US05455269__

Patent Applications on Amiodarone As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to amiodarone: •

Amiodarone solutions suitable for intravenous administration Inventor(s): Fawzi, Mahdi B.; (Morristown, NJ), Lee, Yong J.; (Monroe, NY), Ofslager, Christian L.; (Newburgh, NY), Shah, Syed M.; (East Hanover, NJ) Correspondence: Wyeth; Patent Law Group; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030139468 Date filed: January 22, 2002 Abstract: Parenteral solutions suitable for intravenous injection are provided comprising amiodarone in an amount of from 0.9 mg/ml to 30 mg/ml, a lactic acid buffer and water, the solution having a pH of 2.5 to 4.5.

9

This has been a common practice outside the United States prior to December 2000.

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Excerpt(s): The present invention is directed to parenteral formulations of amiodarone suitable for intravenous administration. More specifically, the present invention is directed to parenteral solutions comprising amiodarone and a lactic acid buffer. 2-nbutyl-3-(3,5-diiodo-4-(.beta.-N-diethylaminoethoxy)benzoyl) benzofuran (hereinafter "amiodarone") is useful as an antiarrhythmic agent. Amiodarone has been approved in the United States for the treatment of life-threatening ventricular tachycardia. Amiodarone is highly insoluble in water and thus, attempts to develop aqueous formulations suitable for intravenous administration have not always been successful. The commercially available intravenous formulation of amiodarone (Cordarone.RTM. IV manufactured and sold by Wyeth-Ayerst Pharmaceuticals) utilizes the surfactant polysorbate 80 and benzyl alcohol to dissolve and solublize the amiodarone. However, the use of polysorbate 80 and other surfactants in intravenous formulations may have undesirable side effects that limit their usefulness. Accordingly, attempts have been made to develop a surfactant-free amiodarone intravenous formulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Formulations containing amiodarone and sulfoalkyl ether cyclodextrin Inventor(s): Gayed, Atef A.; (Overland Park, KS), Johnson, Karen T.; (Lawrence, KS), Mosher, Gerold L.; (Kansas City, MO) Correspondence: Innovar, L.L.C.; P.O. Box 250647; Plano; TX; 75025-0647; US Patent Application Number: 20030216353 Date filed: May 4, 2002 Abstract: The present invention provides aqueous parenteral formulations containing an antiarrhythmic agent, such as amiodarone, and a sulfoalkyl ether cyclodextrin. The liquid formulations are clear, sterilizable, and chemically and physically stable. The liquid formulations do not require a surfactant and do not precipitate upon dilution with distilled water or other pharmaceutically acceptable liquid carrier. The sulfoalkyl ether cyclodextrin-containing formulation provides significant advantages over other cyclodextrin-containing formulations of amiodarone. The formulation can be prepared in acidic, neutral and slightly basic medium while providing acceptable concentrations of amiodarone suitable for parenteral administration. An SAE-CD-containing formulation of amiodarone can be provided in liquid form or as a reconstitutable powder. Moreover, highly concentrated solutions exceeding 200 mg of amiodarone per mL can be prepared. Solutions can be made either dilutable or non-dilutable with water at room temperature or under conditions typically encountered in the clinic. Excerpt(s): The present invention relates to improved antiarrhythmic formulations and in particular to a parenteral formulation containing amiodarone and a sulfoalkyl ether cyclodextrin and to its use in the treatment of cardiac disorders. Antiarrhythmic drugs are commonly divided into four classes according to their electro-physiological mode of action (Edvardsson, Current Therapeutic Research, Vol. 28, No. 1 Supplement, pages 113S-118S (July 1980); Keefe et al, Drugs, Vol. 22, pages 363-400 (1981); VaughnWilliams, "Classification of Anti-Arrhythmic Drugs in Symposium of Cardiac Arrhythmias", pages 449-472 (Sandoe et al, (eds.) A. B. Astra, Soederlaije, Sweden (1970)). Antiarrhythmic drugs are classified as follows: Class I--local anesthetic effect; Class II--beta-receptor blockade; Class III--prolongation of action potential duration; and Class IV--calcium antagonist. Although it is generally considered a Class III antiarrhythmic drug, amiodarone possesses electrophysiologic characteristics of all four Vaughn-Williams classes: it blocks sodium channels at rapid pacing frequencies (Class

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I); it exerts a noncompetitive antisympathetic action (Class II); it prolongs the duration of the cardiac action potential (Class III); and it exhibits negative chronotropic effects on nodal tissues. Amiodarone possesses sustained efficacy against ventricular and supraventricular tachycardiarrhythmias. Amiodarone also exhibits vasodilatory action, which can decrease cardiac workload and consequently decrease myocardial oxygen consumption, and thus can be used to treat hypertension. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treating pulmonary fibrosis Inventor(s): Uhal, Bruce D.; (East Lansing, MI) Correspondence: Marshall, Gerstein & Borun; 6300 Sears Tower; 233 South Wacker; Chicago; IL; 60606-6357; US Patent Application Number: 20030113330 Date filed: January 6, 2003 Abstract: The present invention relates to uses of non-thiol ACE inhibitors, angiotensin II antagonists, angiotensin II receptor antagonists, endonuclease inhibitors, and caspaseinhibitors to treat pulmonary fibrosis and/or inhibit pulmonary epithelial cell apoptosis, including pulmonary fibrosis associated with amiodarone product toxicity. Excerpt(s): This application claims priority of U.S. Serial No. 60/164,052 filed Nov. 8, 1999, the entire disclosure of which is incorporated by reference herein. The present invention relates generally to novel therapeutic methods for treating pulmonary fibrosis using compounds that inhibit apoptosis of cells mediated by the renin-angiotensinaldosterone system. Intact alveolar epithelium is critical in maintaining many lung functions including gas exchange, water balance, surfactant synthesis and local immunomodulation. Damage to the human lung can result from either blood-borne or inhaled toxicants or by inflammation of extrapulmonary origin, such as that associated with sepsis, although injury by inhalation is the most common mechanism. Studies have documented and detailed the lung injuries induced by a variety of mineral dusts, see, e.g., Miller et al., Environ Health Perspect. 85:15-23 (1990), oxidant gases, see, e.g., Evans et al., Arch. Environ. Health 24:180-188 (1972), and cytotoxic drugs, see, e.g., Thrall et al., Am. J. Pathol. 95:117-130 (1979). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Premixed amiodarone parenteral solution and method for making the same Inventor(s): Doty, Mark J.; (Grayslake, IL), Kipp, James E.; (Wauconda, IL), Raghaven, Neervalur V.; (Northbrook, IL), Rebbeck, Christine L.; (Algonquin, IL) Correspondence: Wallenstein & Wagner, Ltd; 311 S. Wacker Drive, 53rd Floor; Chicago; IL; 60606-6630; US Patent Application Number: 20020143050 Date filed: August 31, 2001 Abstract: A premix parenteral solution for intravenous administration having amiodarone, as an active ingredient, solubilized in a solution of water for injection and about 0.4-12 mg/ml of a non-ionic surfactant to a concentration range of from 0.2 to 6 mg/ml is disclosed. The solution optionally may include an osmotic agent. No dilution

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of the solution is required before administering to a patient and the sterile packaged solution has an initial pH within the range of from about 2.9 to about 3.2, preferably about 3.1. Additionally, a method for producing an amiodarone solution suitable for intravenous administration is further disclosed. Excerpt(s): The present application is a continuation-in-part of U.S. patent application Ser. No. 09/822,767, filed on Mar. 29, 2001, which is expressly incorporated herein by reference. This invention relates generally to a premixed pharmaceutical composition containing amiodarone for parenteral administration. Particularly, the composition, and method for making the same, provides an enhanced shelf-life and an improved polymeric container compatibility over diluted formulations. Amiodarone HCl (2-butyl3-benzofuranyl) [4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone hydrochloride, is a class III antiarrhythmic agent that possesses electro physiologic characteristics of all four Vaughan Williams classes. The hydrochloride salt is currently marketed in ampoules suitable for intravenous administration following dilution in dextrose (CORDARONE.RTM. IV, Wyeth-Ayerst). Each milliliter of a CORDARONE.RTM. ampoule contains 50 mg amiodarone HCl, 20.2 mg benzyl alcohol, 100 mg polysorbate 80, and water for injection. The pH of the commercial product after dilution in dextrose is approximately 3.8-4.0. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with amiodarone, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “amiodarone” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on amiodarone. You can also use this procedure to view pending patent applications concerning amiodarone. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON AMIODARONE Overview This chapter provides bibliographic book references relating to amiodarone. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on amiodarone include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Chapters on Amiodarone In order to find chapters that specifically relate to amiodarone, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and amiodarone using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “amiodarone” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on amiodarone: •

Drugs and the Liver Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.335-363. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: The liver is particularly concerned with drug metabolism, and especially of drugs given orally. Drugs can cause toxic effects that can mimic almost every naturally occurring liver disease in man. This chapter on drugs and the liver is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter is organized into specific pathologies and their potential causes: hepato-cellular zone 3 necrosis, due to carbon tetrachloride, Amanita mushrooms, paracetamol (acetaminophen), salicylates, hyperthermia, hypothermia, and burns;

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hepato-cellular zone 1 necrosis, due to ferrous sulfate or phosphorus; mitochondrial cytopathies, due to sodium valproate, tetracyclines, tacrine, antiviral nucleoside analogues, and Bacillus cereus; steatohepatitis, due to perhexiline maleate, amiodarone, synthetic estrogens, and calcium channel blockers; fibrosis, due to methotrexate, other cytotoxic drugs, arsenic, vinyl chloride, vitamin A, and retinoids; vascular changes, due to sinusoidal dilatation, peliosis hepatitis, and veno-occlusive disease (VOD); acute hepatitis, due to isoniazid, methyl dopa, halothane, hydrofluorocarbons, systemic antifungals, oncology drugs, nervous system modifiers, sustained-release nicotinic acid (niacin), sulfonamides and derivatives, nonsteroidal anti-inflammatory drugs, antithyroid drugs, quinidine and quinine, troglitazone, and anti-convulsants; chronic hepatitis, due to herbal remedies and recreational drugs; canalicular cholestasis, due to cyclosporine A and ciprofloxacin; hepato-canalicular cholestasis, due to chlorpromazine, penicillins, sulfonamides, erythromycin, haloperidol, cimetidine and ranitidine, oral hypoglycemic agents, tamoxifen, other causes, and dextropropoxyphene; ductular cholestasis; biliary sludge; sclerosing cholangitis; hepatic nodules and tumors; and hepatocellular carcinoma (HCC, liver cancer). 28 figures. 5 tables. 170 references.

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CHAPTER 6. PERIODICALS AND NEWS ON AMIODARONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover amiodarone.

News Services and Press Releases One of the simplest ways of tracking press releases on amiodarone is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “amiodarone” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to amiodarone. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “amiodarone” (or synonyms). The following was recently listed in this archive for amiodarone: •

Intermittent dobutamine plus daily amiodarone helpful in refractory heart failure Source: Reuters Industry Breifing Date: April 28, 2004

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Benefits of amiodarone for sinus rhythm offset by side effects Source: Reuters Industry Breifing Date: February 25, 2004

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Glenmark sees amiodarone exports at $4-$6 million Source: Reuters Industry Breifing Date: November 27, 2003

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Low-dose amiodarone acts synergistically with azole drugs to kill fungi Source: Reuters Industry Breifing Date: June 18, 2003

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Two amiodarone regimens reduce atrial fibrillation risk after open-heart surgery Source: Reuters Industry Breifing Date: August 12, 2002

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Addition of irbesartan to amiodarone reduces recurrence of atrial fibrillation Source: Reuters Industry Breifing Date: June 24, 2002

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Thyroid effects of amiodarone can usually be managed conservatively Source: Reuters Medical News Date: March 26, 2002

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APP gets tentative nod for generic Cordarone injection, files for IPO Source: Reuters Industry Breifing Date: October 04, 2001

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Dofetilide appears superior to amiodarone for patients with heart failure Source: Reuters Industry Breifing Date: July 04, 2001

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Oral amiodarone reduces AF in older patients after open-heart surgery Source: Reuters Industry Breifing Date: March 15, 2001

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Barr gets US approval to market Cordarone generic Source: Reuters Industry Breifing Date: January 29, 2001

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Low-dose amiodarone prevents recurrence of atrial fibrillation Source: Reuters Medical News Date: March 30, 2000

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High-dose amiodarone helpful in conversion of some cases of atrial fibrillation Source: Reuters Medical News Date: January 05, 2000

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Concurrent amiodarone therapy not a contraindication to CHF treatment with carvedilol Source: Reuters Medical News Date: November 25, 1999

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Heart drug amiodarone reduces cardiac arrest deaths Source: Reuters Health eLine Date: September 16, 1999

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Preoperative Amiodarone Protects Against A Fib After Cardiac Surgery Source: Reuters Medical News Date: December 18, 1997

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Low-Dose Amiodarone Use Not Without Risks Source: Reuters Medical News Date: September 03, 1997

Periodicals and News

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Benefits Of Amiodarone In CHF Patients Limited To Patients With Elevated Heart Rates Source: Reuters Medical News Date: May 01, 1997

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IV Amiodarone Is Effective For Refractory Ventricular Arrhythmia Source: Reuters Medical News Date: December 01, 1995

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Anticoagulants And Amiodarone Effective in AMI Patients Source: Reuters Medical News Date: March 24, 1995

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “amiodarone” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “amiodarone” (or synonyms). If you know the name of a company that is relevant to amiodarone, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “amiodarone” (or synonyms).

Academic Periodicals covering Amiodarone Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to amiodarone. In addition to these sources, you can search for articles covering amiodarone that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for amiodarone. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with amiodarone. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to amiodarone: Amiodarone •

Systemic - U.S. Brands: Cordarone; Cordarone I.V. http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202029.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “amiodarone” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 6512 12 752 4 232 7512

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “amiodarone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on amiodarone can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to amiodarone. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to amiodarone. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “amiodarone”:

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Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Cardiomyopathy http://www.nlm.nih.gov/medlineplus/cardiomyopathy.html Dental Health http://www.nlm.nih.gov/medlineplus/dentalhealth.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html Herbal Medicine http://www.nlm.nih.gov/medlineplus/herbalmedicine.html Pacemakers and Implantable Defibrillators http://www.nlm.nih.gov/medlineplus/pacemakersandimplantabledefibrillators.ht l Pulmonary Embolism http://www.nlm.nih.gov/medlineplus/pulmonaryembolism.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to amiodarone. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

Patient Resources

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to amiodarone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with amiodarone. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about amiodarone. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “amiodarone” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “amiodarone”. Type the following hyperlink into your

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Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “amiodarone” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “amiodarone” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

21

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

22

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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AMIODARONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is

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present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allium: A genus of liliaceous herbs containing onions (Allium cepa), garlic (Allium sativum), and others; many produce pungent, often bacteriostatic and physiologically active compounds and are used as food, condiment, and medicament, the latter in traditional medicine. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy,

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magnet therapy, spiritual healing, and meditation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Ampoule: A small glass or plastic container capable of being sealed so as to preserve its contents in a sterile condition; used principally for containing sterile parenteral solutions (American English: ampule). [EU] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful

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situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU]

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Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arrhythmogenic: Producing or promoting arrhythmia. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion

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channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [NIH]

Atrial Function: The hemodynamic and electrophysiological action of the atria. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a

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local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Bepridil: Beta-((2-Methylpropoxy)methyl)-N-phenyl-N-(phenylmethyl)-1pyrrolidineethanamine. A long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH]

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Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the

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drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [NIH]

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Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DCshock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chloral Hydrate: A hypnotic and sedative used in the treatment of insomnia. The safety margin is too narrow for chloral hydrate to be used as a general anesthetic in humans, but it is commonly used for that purpose in animal experiments. It is no longer considered useful as an anti-anxiety medication. [NIH] Chloralose: A derivative of chloral hydrate that was used as a sedative but has been replaced by safer and more effective drugs. Its most common use is as a general anesthetic in animal experiments. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla.

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[NIH]

Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronotropic: Affecting the time or rate, as the rate of contraction of the heart. [EU] Cimetidine: A histamine congener, it competitively inhibits histamine binding to H2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output. It also blocks the activity of cytochrome P450. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clavulanic Acid: Clavulanic acid (C8H9O5N) and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is

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differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective

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tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid

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leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarin: A fluorescent dye. [NIH] Criterion: A standard by which something may be judged. [EU] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Retinitis: Infection of the retina by cytomegalovirus characterized by retinal necrosis, hemorrhage, vessel sheathing, and retinal edema. Cytomegalovirus retinitis is a major opportunistic infection in AIDS patients and can cause blindness. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH]

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Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Defibrillation: The act to arrest the fibrillation of (heart muscle) by applying electric shock across the chest, thus depolarizing the heart cells and allowing normal rhythm to return. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops

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(mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] DNA Damage: Drug- or radiation-induced injuries in DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions which interfere with replication and transcription, as well as point mutations which disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair). If the damage is extensive, it can induce apoptosis. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject

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nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack

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of nutrition. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encainide: An effective and generally well-tolerated anti-arrhythmia agent for suppressing all forms of ventricular arrhythmia. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, encainide exacerbates the arrhythmia and is not recommended for use in these patients. The drug is a potent blocker of sodium channels and produces marked slowing of conduction within the His-Purkinje system and myocardium. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured

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spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Epidemics: A period of increased prevalence of a particular disease in a population. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling

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reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flatus: Gas passed through the rectum. [NIH] Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flutter: A rapid vibration or pulsation. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Foscarnet: An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH]

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Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genital: Pertaining to the genitalia. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Griseofulvin: An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haloperidol: Butyrophenone derivative. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or

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public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Heartbeat: One complete contraction of the heart. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoptysis: Bronchial hemorrhage manifested with spitting of blood. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU]

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Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Hospital Charges: The prices a hospital sets for its services. Hospital costs (the direct and indirect expenses incurred by the hospital in providing the services) are one factor in the determination of hospital charges. Other factors may include, for example, profits, competition, and the necessity of recouping the costs of uncompensated care. [NIH] Hospital Costs: The expenses incurred by a hospital in providing care. The hospital costs attributed to a particular patient care episode include the direct costs plus an appropriate proportion of the overhead for administration, personnel, building maintenance, equipment, etc. Hospital costs are one of the factors which determine hospital charges (the price the hospital sets for its services). [NIH] Hospital Mortality: A vital statistic measuring or recording the rate of death from any cause in hospitalized populations. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrops Fetalis: Edema of the entire body due to abnormal accumulation of serous fluid in the tissues, associated with severe anemia and occurring in fetal erythroblastosis. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart

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walls, interfering with the heart's ability to fill with and pump blood. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate

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agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques.

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[EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iopanoic Acid: Radiopaque medium used as diagnostic aid. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is

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rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver Mitochondria: Yellow discoloration of the liver due to fatty degeneration of liver parenchymal cells; the cause may be chemical poisoning. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loratadine: A second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines it lacks central nervous system depressing effects such as drowsiness. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH]

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Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies

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(usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired

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from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense

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pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU]

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Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncology: The study of cancer. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Orlistat: A lipase inhibitor used for weight loss. Lipase is an enzyme found in the bowel that assists in lipid absorption by the body. Orlistat blocks this enzyme, reducing the amount of fat the body absorbs by about 30 percent. It is known colloquially as a "fat blocker." Because more oily fat is left in the bowel to be excreted, Orlistat can cause an oily anal leakage and fecal incontinence. Orlistat may not be suitable for people with bowel conditions such as irritable bowel syndrome or Crohn's disease. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ownership: The legal relation between an entity (individual, group, corporation, or-profit, secular, government) and an object. The object may be corporeal, such as equipment, or completely a creature of law, such as a patent; it may be movable, such as an animal, or immovable, such as a building. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH]

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Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perhexiline: 2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH]

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Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Photoallergy: Sensitization of the skin to light usually due to the action of certain substances or drugs, may occur shortly after exposure to a substance or after a latent period of from days to months. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Pneumonectomy: An operation to remove an entire lung. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in

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biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysorbates: Sorbitan mono-9-octadecanoate poly(oxy-1,2-ethanediyl) derivatives; complex mixtures of polyoxyethylene ethers used as emulsifiers or dispersing agents in pharmaceuticals. [NIH] Postoperative: After surgery. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Pregnancy Maintenance: Physiological mechanisms that sustain the state of pregnancy. [NIH]

Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH]

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Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [NIH]

Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region.

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Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation

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therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH]

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Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH]

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Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH]

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Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skin Pigmentation: Coloration of the skin. [NIH] Sludge: A clump of agglutinated red blood cells. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH]

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Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Sotalol: An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Squamous: Scaly, or platelike. [EU] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Subacute: Somewhat acute; between acute and chronic. [EU]

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Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppository: A medicated mass adapted for introduction into the rectal, vaginal, or urethral orifice of the body, suppository bases are solid at room temperature but melt or dissolve at body temperature. Commonly used bases are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU]

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Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachyarrhythmia: Tachycardia associated with an irregularity in the normal heart rhythm. [EU]

Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyrotoxicosis: The clinical syndrome that reflects the response of the peripheral tissues to an excess of thyroid hormone. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a

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specific function. [NIH] Tocainide: An antiarrhythmic agent which exerts a potential- and frequency-dependent block of sodium channels. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Torsades de Pointes: A ventricular tachycardia characterized by periodic twisting of the points of the QRS complexes and rates between 200 and 250 beats per minute. It may be selflimited or may progress to ventricular fibrillation. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH]

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Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH]

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Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vindesine: Vinblastine derivative with antineoplastic activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus, head, and neck, and Hodgkin's and non-Hodgkin's lymphomas. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border

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of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH]

159

INDEX A Ablate, 111, 120 Ablation, 9, 26, 49, 111 Abscess, 111, 150 Acceptor, 111, 137, 142 Acetaminophen, 4, 69, 83, 111 Acne, 111, 149 Acquired Immunodeficiency Syndrome, 74, 111 Acute leukemia, 111, 157 Adaptability, 111, 120 Adaptation, 111, 120, 140 Adenine, 111 Adenocarcinoma, 111, 132 Adenosine, 68, 111, 113, 144 Adrenal Cortex, 111, 112, 146 Adrenergic, 111, 112, 115, 126, 129, 139, 147, 152, 153 Adverse Effect, 22, 29, 111, 151, 157 Aerobic, 111, 139 Aerosol, 31, 52, 112, 157 Aetiology, 18, 112 Affinity, 112, 115, 137, 151 Agonist, 112, 126, 154 Albumin, 112, 139 Aldosterone, 81, 112 Algorithms, 112, 117 Alimentary, 112, 136, 143 Alkaline, 112, 118 Alkaloid, 112, 140, 147 Allergic Rhinitis, 112, 137 Allium, 30, 31, 112 Alprenolol, 112, 139 Alternative medicine, 87, 112 Amine, 113, 132 Amino Acids, 113, 114, 129, 143, 145, 146, 155 Amoxicillin, 3, 113 Ampicillin, 113 Ampoule, 82, 113 Ampulla, 113, 120 Anabolic, 113 Anaesthesia, 51, 113, 134 Anal, 113, 140, 142 Analgesic, 111, 113, 136, 140, 142, 147 Analog, 113, 136 Anaphylactic, 75, 113 Anaphylaxis, 113

Anatomical, 113, 116, 125, 134, 139 Anemia, 113, 117, 133, 154 Anesthesia, 24, 36, 47, 53, 113, 145 Aneurysm, 113, 156 Angina, 113, 114, 139, 143 Angina Pectoris, 113, 139 Anginal, 112, 114, 117, 141 Angiotensinogen, 114, 149 Anomalies, 114, 140, 154 Antagonism, 11, 114, 126 Antianginal, 113, 114 Antiarrhythmic, 34, 36, 44, 45, 49, 60, 61, 65, 67, 69, 74, 75, 78, 80, 82, 113, 114, 139, 155 Antibacterial, 74, 114, 121, 136, 152 Antibiotic, 113, 114, 116, 118, 121, 125, 127, 129, 131, 152 Antibody, 112, 114, 122, 124, 128, 132, 134, 135, 136, 138, 140, 148, 158 Anticoagulant, 50, 114, 157 Anticonvulsant, 114, 139 Antidepressant, 114, 130 Antidiuretic, 52, 114 Antiemetic, 114, 115, 120 Antifungal, 74, 114, 131 Antigen, 112, 113, 114, 122, 128, 132, 133, 134, 135, 138, 139 Antihypertensive, 112, 114, 117 Anti-inflammatory, 3, 84, 111, 114, 125, 131, 150 Anti-Inflammatory Agents, 3, 114 Antimetabolite, 114, 139 Antimicrobial, 114, 121 Antineoplastic, 114, 127, 139, 157 Antioxidant, 70, 115, 142, 151 Antipsychotic, 115, 120 Antipyretic, 111, 115, 147 Antiviral, 84, 115, 130 Anxiety, 8, 115, 120 Aorta, 115, 119, 123, 156 Apoptosis, 81, 115, 120, 126 Aqueous, 32, 37, 38, 52, 77, 80, 115, 116, 124 Arrhythmogenic, 43, 115 Arterial, 115, 123, 133, 146, 154 Arteries, 115, 118, 123, 140 Arterioles, 115, 118, 119, 156

160

Amiodarone

Artery, 47, 48, 51, 54, 55, 113, 115, 123, 128, 130, 147, 149 Assay, 33, 42, 54, 115, 134 Astrocytes, 115, 139, 140 Asymptomatic, 11, 15, 116, 117, 128, 130 Atrial, 9, 12, 13, 14, 16, 19, 20, 21, 23, 24, 25, 26, 35, 36, 37, 39, 40, 41, 43, 45, 46, 47, 48, 49, 50, 55, 61, 67, 75, 76, 77, 86, 113, 116, 123, 130, 157 Atrial Flutter, 24, 67, 116 Atrial Function, 16, 116 Atrioventricular, 15, 17, 116, 123, 153 Atrioventricular Node, 116, 153 Atrium, 116, 119, 123, 153, 156 Attenuated, 116, 126 Autonomic Nervous System, 116, 153 Azithromycin, 17, 49, 116 B Babesiosis, 116, 147 Bacteria, 114, 116, 128, 139, 150, 152, 155, 156 Bacteriostatic, 112, 116, 129 Barbiturate, 116, 123 Base, 74, 111, 116, 126, 129, 136, 144 Benign, 38, 116, 141, 148 Benzyl Alcohol, 77, 80, 82, 116 Bepridil, 36, 117 Beta blocker, 24, 25, 43, 79, 117 Beta-Thalassemia, 33, 117 Bile, 117, 120, 130, 136, 137, 152 Bile duct, 117, 120 Bile Pigments, 117, 136 Biliary, 83, 117, 120 Bioavailability, 17, 76, 117 Biochemical, 20, 56, 68, 114, 117, 143, 150 Biopsy, 117, 143 Biosynthesis, 117, 137, 151 Biotechnology, 11, 12, 87, 95, 117 Biotransformation, 117 Blastocyst, 117, 144 Blood Coagulation, 117, 118 Blood Glucose, 118, 132, 134 Blood pressure, 114, 118, 133, 134, 140, 141, 151, 156 Blood vessel, 117, 118, 119, 120, 123, 128, 136, 137, 151, 152, 156 Blood-Brain Barrier, 118, 136, 154 Body Fluids, 118, 151 Bone Marrow, 54, 111, 118, 124, 134, 137, 140, 152 Boron, 118, 124 Bowel, 113, 118, 142

Brachytherapy, 118, 135, 136, 148, 158 Brain Stem, 118, 123 Breast Feeding, 13, 118 Broad-spectrum, 113, 118 Bronchi, 118, 129, 136, 155 Bronchial, 118, 132 Bronchitis, 118, 121 Bronchodilator, 118, 136 Buccal, 118, 137 Bupivacaine, 118, 137 C Calcium, 80, 84, 117, 118, 119, 122, 126, 141, 157 Calcium Channel Blockers, 84, 118 Calmodulin, 117, 119 Candidiasis, 74, 119 Candidosis, 119 Capillary, 42, 119, 157 Capsules, 119, 126 Carbohydrate, 119, 131 Carbon Dioxide, 119, 125, 131, 144, 149 Carcinogenic, 119, 135, 152 Carcinoma, 15, 119, 157 Cardiac arrest, 52, 86, 119, 153 Cardiomyopathy, 19, 45, 75, 100, 119 Cardiopulmonary, 61, 119 Cardiopulmonary Bypass, 61, 119 Cardiotonic, 119, 125, 126 Cardiotoxicity, 69, 119 Cardiovascular System, 78, 119 Cardioversion, 9, 12, 14, 16, 36, 47, 50, 61, 119 Case report, 34, 42, 44, 56, 120 Caspase, 81, 120 Catecholamine, 120, 126 Catheter, 9, 12, 120 Catheter Ablation, 9, 12, 120 Causal, 120, 149 Cell Count, 18, 120 Cell Death, 69, 115, 120, 141 Cell membrane, 118, 120, 129, 145, 151 Cell Respiration, 120, 139, 149 Central Nervous System, 116, 120, 130, 137, 139, 140, 150, 154 Cerebrovascular, 119, 120 Character, 3, 113, 120, 125 Chemotherapy, 65, 74, 120, 157 Chloral Hydrate, 120 Chloralose, 61, 120 Chlorpromazine, 84, 120 Cholangitis, 84, 120 Cholestasis, 84, 120

161

Cholesterol, 117, 121, 137, 150, 151, 152, 154 Chromatin, 115, 121, 138 Chronic, 19, 20, 26, 32, 39, 45, 46, 50, 51, 60, 61, 84, 121, 135, 146, 147, 152, 154 Chronic Obstructive Pulmonary Disease, 51, 121 Chronotropic, 81, 121 Cimetidine, 84, 121 Cinchona, 121, 147 Ciprofloxacin, 84, 121 Cirrhosis, 40, 121 Clavulanic Acid, 3, 121 Clinical Medicine, 35, 121, 145 Clinical trial, 4, 6, 7, 8, 9, 41, 95, 121, 123, 124, 126, 127, 140, 146, 148 Clonic, 121, 123 Cloning, 117, 121 Coagulation, 117, 121, 157 Coenzyme, 121, 137, 151 Collagen, 67, 121, 146 Colloidal, 78, 112, 122, 127 Complement, 122 Complementary and alternative medicine, 65, 71, 122 Complementary medicine, 65, 122 Computational Biology, 95, 122 Concomitant, 22, 122 Conduction, 17, 76, 116, 120, 122, 128 Congenita, 122, 147 Congestive heart failure, 5, 7, 9, 10, 25, 33, 39, 67, 75, 122 Conjugated, 122, 124 Connective Tissue, 118, 121, 122, 123, 130, 154 Contamination, 123, 132 Contractility, 123, 127 Contraindications, ii, 123 Contralateral, 123, 138 Control group, 123, 145, 148 Controlled study, 25, 40, 123 Conventional treatment, 7, 123 Convulsants, 84, 123 Convulsions, 114, 116, 123 Cor, 123 Coronary, 14, 24, 25, 36, 47, 48, 51, 54, 55, 61, 78, 79, 114, 116, 117, 123, 140, 143 Coronary Artery Bypass, 14, 24, 25, 36, 61, 123 Coronary Thrombosis, 79, 123, 140 Corticosteroids, 27, 123, 131 Cortisone, 124, 125

Coumarin, 17, 124 Criterion, 5, 124 Cryptococcosis, 74, 124 Cryptosporidiosis, 116, 124 Curative, 124, 141, 154 Curcumin, 69, 124 Cutaneous, 19, 45, 74, 119, 124, 137, 144 Cyclosporine, 84, 124 Cytochrome, 36, 68, 121, 124 Cytokines, 67, 124, 139 Cytomegalovirus, 124, 130 Cytomegalovirus Retinitis, 124, 130 Cytoplasm, 115, 120, 124, 138, 154 Cytotoxic, 4, 81, 84, 124, 148 Cytotoxicity, 60, 67, 124 D Data Collection, 5, 125 Daunorubicin, 125, 127 Decarboxylation, 125, 132 Decidua, 125, 144 Defibrillation, 32, 34, 60, 125 Degenerative, 125, 132 Deletion, 115, 125 Delivery of Health Care, 125, 131 Dementia, 111, 115, 125 Dendrites, 125, 141 Dermatitis, 27, 125 Dexamethasone, 28, 125 Diagnostic procedure, 73, 87, 125 Diastolic, 125, 133 Dietary Fats, 125, 137 Diffusion, 125, 126 Digestion, 112, 117, 118, 125, 137, 152 Digitalis, 66, 125 Dilatation, Pathologic, 125, 156 Dilated cardiomyopathy, 15, 26, 27, 32, 45, 125 Dilation, 125, 156 Diltiazem, 24, 25, 60, 126 Dilution, 74, 80, 81, 82, 126 Direct, iii, 4, 61, 62, 89, 119, 120, 121, 126, 133, 147, 149, 153 Disposition, 23, 55, 126 Dissociation, 112, 126, 136 Distal, 120, 123, 126, 146 DNA Damage, 69, 126 Dobutamine, 39, 85, 126 Dopa, 84, 126, 136 Dopamine, 6, 115, 120, 126, 136, 140, 141 Dosage Forms, 76, 77, 126 Dose-dependent, 23, 55, 126 Double-blind, 35, 39, 126, 127

162

Amiodarone

Double-blinded, 35, 127 Doxorubicin, 60, 65, 67, 68, 69, 127 Drug Interactions, 36, 90, 127 Drug Resistance, 69, 127 Drug Tolerance, 127, 155 Dyes, 78, 127 Dyspnea, 127, 147 E Ectopic, 54, 60, 127 Efficacy, 4, 7, 11, 12, 26, 27, 38, 39, 41, 49, 55, 60, 61, 75, 81, 127 Ejection fraction, 5, 7, 9, 10, 127 Elastic, 127, 152, 153 Elastin, 122, 127 Elective, 127 Electric shock, 125, 127 Electrolyte, 112, 127, 145, 151 Electrons, 115, 116, 127, 136, 142, 147, 148 Electrophoresis, 42, 127 Emaciation, 111, 127 Emboli, 9, 128, 157 Embolism, 128, 147, 157 Embolization, 9, 128, 157 Embolus, 128, 135 Embryo, 117, 128, 134 Embryology, 128, 130 Emphysema, 44, 121, 128 Empirical, 39, 128 Encainide, 45, 128 Endocarditis, 119, 128 Endogenous, 126, 128 Endothelial cell, 70, 118, 128 Environmental Exposure, 6, 128 Environmental Health, 94, 96, 128 Enzymatic, 118, 122, 128, 132 Enzyme, 21, 61, 120, 121, 128, 133, 137, 140, 142, 143, 149, 151, 153, 157 Enzyme-Linked Immunosorbent Assay, 21, 128 Epidemics, 43, 129 Epidermis, 129, 133 Epinephrine, 111, 126, 129, 136, 141, 156 Epithelial, 81, 111, 125, 129 Epithelial Cells, 129 Epithelium, 81, 129 Erythrocytes, 113, 116, 118, 129, 148 Erythromycin, 84, 116, 129 Esophagus, 129, 152, 157 Estrogen, 129, 150, 154 Ether, 80, 129 Excipients, 129, 145 Excitability, 129, 147

Excitation, 116, 129, 141 Exocytosis, 129, 154 Exogenous, 117, 128, 129 External-beam radiation, 129, 136, 147, 158 Extracellular, 115, 123, 129, 151 Extraction, 33, 129 Extrapyramidal, 115, 126, 129 F Family Planning, 95, 129 Fat, 118, 123, 128, 130, 137, 142, 152, 153, 156 Fatigue, 130, 132 Femoral, 119, 130 Femoral Artery, 119, 130 Fetal Heart, 8, 130 Fetus, 130, 144 Fibrillation, 5, 12, 13, 14, 16, 19, 20, 21, 23, 24, 25, 26, 35, 36, 37, 39, 40, 41, 43, 45, 46, 47, 48, 49, 50, 55, 61, 75, 76, 77, 86, 116, 125, 130, 157 Fibrosis, 81, 84, 130, 147 Flatus, 130 Flecainide, 22, 30, 45, 55, 130 Fluoxetine, 26, 130 Flutter, 20, 25, 130 Fold, 75, 130 Foscarnet, 4, 130 Free Radicals, 115, 126, 130 Fungus, 119, 124, 130 G Gallbladder, 117, 130 Ganglia, 115, 130, 141, 153 Gas, 81, 119, 125, 130, 131, 133, 136, 149, 157 Gas exchange, 81, 131, 149 Gastric, 113, 121, 126, 131, 132, 143, 148 Gastric Acid, 113, 121, 131 Gastrin, 121, 131, 133 Gastrointestinal, 31, 121, 129, 131, 148, 150, 153 Gene, 60, 117, 131 Gene Expression, 60, 131 Genital, 121, 131 Gestation, 131, 144 Ginseng, 71, 131 Gland, 111, 124, 131, 143, 150, 152, 154 Glucocorticoid, 125, 131 Gluconeogenesis, 131 Glycogen, 131 Glycoprotein, 67, 131 Gonadal, 131, 152

163

Governing Board, 131, 145 Graft, 21, 36, 131 Grafting, 14, 24, 123, 131, 134 Griseofulvin, 4, 131 H Habitual, 120, 131 Haloperidol, 84, 131 Health Care Costs, 7, 8, 131, 132 Health Expenditures, 131 Heart failure, 5, 7, 8, 9, 10, 16, 19, 22, 24, 25, 30, 32, 39, 40, 43, 75, 85, 86, 132, 147 Heart Transplantation, 14, 20, 24, 28, 61, 132 Heartbeat, 132, 153, 157 Hemodynamics, 9, 32, 132 Hemoglobin, 113, 117, 129, 132, 154 Hemoptysis, 56, 132 Hemorrhage, 124, 132 Hepatic, 3, 28, 31, 42, 55, 84, 112, 132, 151 Hepatitis, 13, 49, 53, 84, 132, 143 Hepatitis A, 13, 53, 132 Hepatocellular, 84, 132 Hepatocellular carcinoma, 84, 132 Hepatocyte, 120, 132 Hepatotoxicity, 3, 28, 31, 32, 53, 132 Hepatovirus, 132 Heredity, 131, 132 Histamine, 4, 115, 121, 132, 137, 148 Histidine, 132 Homeostasis, 6, 132 Homologous, 132, 153 Hormone, 11, 45, 52, 60, 112, 124, 129, 131, 133, 146, 151, 154 Horseradish Peroxidase, 128, 133 Hospital Charges, 133 Hospital Costs, 24, 133 Hospital Mortality, 24, 133 Hydrogen, 111, 113, 116, 119, 133, 137, 140, 141, 142 Hydrophilic, 78, 133 Hydrops Fetalis, 50, 133 Hydroxylation, 42, 133 Hydroxylysine, 122, 133 Hydroxyproline, 122, 133 Hyperbilirubinemia, 133, 136 Hyperpigmentation, 34, 133 Hypertension, 81, 119, 123, 133, 139 Hyperthermia, 83, 133 Hyperthyroidism, 28, 31, 54, 133 Hypertrophic cardiomyopathy, 27, 34, 40, 133 Hypertrophy, 34, 123, 134

Hypoglycemic, 84, 134 Hypoglycemic Agents, 84, 134 Hypotension, 75, 115, 123, 134 Hypotensive, 38, 75, 134 Hypothermia, 83, 134 I Idiopathic, 26, 32, 45, 134 Imidazole, 132, 134, 148 Immune response, 114, 124, 134, 153, 157 Immunity, 111, 134 Immunization, 134, 145 Immunoassay, 128, 134 Immunodeficiency, 74, 111, 134 Immunosuppressant, 134, 139 Immunosuppression, 134, 142 Impairment, 6, 120, 134, 138 Implant radiation, 134, 135, 136, 148, 158 Implantation, 32, 134 In vitro, 45, 68, 69, 134 In vivo, 35, 36, 45, 69, 134 Incision, 134, 135 Incontinence, 134, 142 Induction, 35, 66, 115, 134, 151 Infancy, 30, 135 Infarction, 11, 12, 16, 38, 54, 79, 135, 149 Infection, 74, 111, 119, 124, 134, 135, 137, 141, 142, 153, 154, 155, 156, 157 Inflammation, 81, 111, 112, 114, 118, 120, 125, 130, 132, 135, 144, 147, 154, 156 Infusion, 39, 60, 74, 135 Ingestion, 78, 135, 144 Inhalation, 81, 112, 135, 144 Initiation, 29, 56, 60, 135 Innervation, 26, 135 Inotropic, 126, 135 Insecticides, 135, 143 Intensive Care, 20, 36, 40, 135 Intermittent, 39, 85, 135 Internal radiation, 135, 136, 147, 158 Interstitial, 118, 135, 136, 158 Intoxication, 22, 135, 158 Intracellular, 118, 135, 145, 146 Intramuscular, 135, 143 Intrinsic, 4, 75, 112, 135 Invasive, 74, 134, 135 Involuntary, 130, 136, 140, 152 Ionization, 21, 136 Ionizing, 128, 136, 148 Ions, 116, 119, 126, 127, 133, 136, 145, 151 Iopanoic Acid, 48, 53, 136 Irradiation, 28, 136, 158 Irrigation, 79, 136

164

Amiodarone

Irritable Bowel Syndrome, 136, 142 Ischemia, 37, 113, 136, 149 Isoniazid, 84, 136 Isoproterenol, 26, 136 J Jaundice, 51, 133, 136 K Kb, 94, 136 Kinetic, 136 L Lesion, 30, 123, 136 Lethal, 9, 10, 136 Leukemia, 127, 136 Levo, 126, 136 Levodopa, 126, 136 Lidocaine, 37, 117, 137, 139 Ligaments, 123, 137 Lipase, 26, 137, 142 Lipid, 137, 142 Lipid A, 137, 142 Lipid Peroxidation, 137, 142 Lipophilic, 26, 75, 137 Liver, 3, 28, 33, 42, 47, 60, 62, 83, 111, 112, 117, 121, 124, 130, 131, 132, 137, 139, 140, 157 Liver cancer, 84, 137 Liver Mitochondria, 62, 137 Liver Neoplasms, 137, 157 Localized, 111, 135, 137, 144, 156 Loratadine, 53, 137 Lovastatin, 137, 151 Lupus, 23, 137, 154 Lymph, 128, 137 Lymphatic, 135, 137, 152 Lymphatic system, 137, 152 Lymphocyte Count, 111, 137 Lymphocytes, 111, 114, 134, 137, 138, 157 Lymphoid, 28, 123, 138 M Maintenance therapy, 12, 138 Malignant, 43, 111, 114, 137, 138, 141, 148 Mammary, 123, 138, 154 Mediate, 126, 138, 148 Mediator, 126, 138, 150 Medical Records, 138, 149 Medical Staff, 127, 138 Medicament, 112, 138 MEDLINE, 95, 138 Meiosis, 138, 153 Melanocytes, 133, 138 Membrane, 6, 112, 115, 120, 122, 126, 129, 138, 140, 142, 147, 151, 154

Membrane Glycoproteins, 138 Memory, 5, 9, 125, 138 Mental, iv, 4, 43, 94, 96, 125, 126, 130, 138, 145, 150 Mental Disorders, 138, 145 Mental Health, iv, 4, 94, 96, 138, 145 Mesencephalic, 6, 138 Meta-Analysis, 21, 25, 138 Metabolite, 4, 36, 61, 68, 117, 137, 139 Methotrexate, 84, 139 Metoprolol, 25, 139 Mexiletine, 38, 45, 139 Microbe, 139, 155 Microglia, 115, 139, 140 Microorganism, 139, 157 Microscopy, 35, 133, 139 Milk Thistle, 139, 151 Milliliter, 82, 139 Mitochondria, 6, 139 Mitochondrial Swelling, 139, 141 Mitosis, 115, 139 Mitotic, 139, 157 Mitoxantrone, 67, 139 Modeling, 55, 139 Modification, 17, 139, 147 Molecular, 4, 35, 38, 61, 95, 97, 117, 119, 122, 140, 144, 153, 155 Molecule, 114, 116, 121, 122, 126, 129, 140, 142, 144, 148 Monitor, 10, 22, 37, 140, 141 Monoamine, 6, 61, 140 Monoclonal, 136, 140, 148, 158 Morphine, 61, 140, 142 Morphology, 67, 140 Mucosa, 137, 140 Multicenter Studies, 9, 140 Multicenter study, 140 Multidrug resistance, 68, 140 Multiple Organ Failure, 49, 140 Multivariate Analysis, 8, 140 Myelosuppression, 140, 157 Myocardial infarction, 8, 10, 15, 27, 36, 42, 48, 66, 79, 123, 126, 140, 157 Myocardium, 38, 114, 128, 140 Myotonia, 140, 147 N Narcotic, 140 Nausea, 114, 115, 126, 140 Necrosis, 83, 115, 124, 135, 140, 141, 149, 150 Neonatal, 13, 29, 44, 141 Neoplasms, 111, 114, 125, 141, 148

165

Nervous System, 84, 116, 120, 138, 141, 153 Neural, 139, 141, 151 Neurons, 6, 125, 130, 137, 141, 153 Neuropathy, 16, 17, 29, 46, 141, 143 Neurotoxicity, 141, 157 Neurotransmitter, 111, 126, 132, 141, 153 Neutrons, 136, 141, 147 Niacin, 84, 141, 156 Nifedipine, 4, 66, 141 Norepinephrine, 111, 126, 141 Nuclear, 26, 27, 30, 31, 127, 141 Nucleus, 115, 116, 121, 124, 138, 141, 146 O Ocular, 56, 141 Oculomotor, 138, 142 Ointments, 126, 142 Oncology, 53, 68, 84, 142 Opiate, 140, 142 Opium, 140, 142 Opportunistic Infections, 74, 111, 142 Orlistat, 26, 142 Osmosis, 142 Osmotic, 81, 112, 139, 142 Outpatient, 5, 7, 142 Overdose, 123, 142 Ownership, 8, 142 Oxidation, 6, 111, 115, 117, 124, 137, 142 Oxidative Stress, 6, 142 Oxygen Consumption, 81, 142, 149 Oxygenator, 119, 142 P Pacemaker, 51, 143 Palliative, 143, 154 Pancreas, 137, 143 Paralysis, 138, 143 Parenteral, 13, 53, 74, 76, 77, 78, 79, 80, 81, 82, 113, 143 Pathologic, 115, 117, 119, 123, 133, 143, 147, 156 Pathologic Processes, 115, 143 Pathologies, 83, 143 Pepsin, 121, 143 Pepsin A, 121, 143 Peptide, 143, 145, 146 Percutaneous, 21, 143 Perhexiline, 84, 143 Pericardium, 143, 154 Pesticides, 6, 135, 143 Pharmaceutical Preparations, 79, 143 Pharmaceutical Solutions, 126, 143 Pharmacodynamics, 67, 143

Pharmacokinetic, 143 Pharmacologic, 47, 113, 144, 155 Phenyl, 117, 144 Phosphorus, 84, 118, 144 Photoallergy, 144 Photosensitivity, 15, 71, 144 Physiologic, 82, 112, 117, 126, 144, 146, 148, 156 Pigmentation, 35, 133, 144 Pilot study, 10, 25, 60, 65, 144 Placenta, 22, 144, 146 Plants, 112, 119, 125, 131, 140, 141, 144, 150, 155 Plasma, 20, 21, 33, 76, 77, 112, 120, 132, 139, 144, 149 Plasmapheresis, 27, 144 Pneumonectomy, 40, 144 Pneumonia, 17, 18, 123, 144 Pneumonitis, 11, 18, 31, 144 Point Mutation, 126, 144 Poisoning, 135, 137, 141, 144 Polyethylene, 75, 144, 153 Polyethylene Glycols, 75, 144, 153 Polymers, 4, 144, 145, 146 Polymorphic, 17, 37, 145 Polypeptide, 121, 143, 145, 154 Polysorbates, 75, 145 Postoperative, 9, 13, 14, 24, 29, 37, 47, 48, 54, 140, 145 Potassium, 76, 112, 145, 147 Potassium Channels, 76, 145 Practice Guidelines, 96, 145 Precursor, 114, 126, 128, 136, 141, 145, 156 Pregnancy Maintenance, 145 Preoperative, 9, 24, 86, 145 Presynaptic, 141, 145, 154 Prevalence, 33, 75, 129, 145 Primary endpoint, 5, 7, 9, 145 Primary Prevention, 7, 8, 10, 16, 145 Procaine, 137, 145 Progesterone, 146, 152 Progressive, 121, 125, 127, 140, 141, 146, 147 Proline, 122, 133, 146 Propafenone, 39, 146 Prophase, 146, 153 Prophylaxis, 41, 47, 51, 66, 146, 149, 157 Prostaglandin, 146 Protective Agents, 119, 146 Protein S, 117, 129, 146 Proteins, 16, 113, 114, 120, 121, 122, 124, 129, 140, 143, 144, 145, 146, 151

166

Amiodarone

Protocol, 9, 146 Proximal, 126, 145, 146, 150 Psoriasis, 146, 149 Psychoactive, 147, 158 Public Policy, 95, 147 Publishing, 11, 147 Pulmonary Artery, 118, 147, 156 Pulmonary Embolism, 100, 147, 157 Pulmonary Fibrosis, 35, 69, 81, 147 Pulsation, 130, 147 Pulse, 140, 147 Q Quality of Life, 5, 7, 9, 147 Quinidine, 60, 61, 84, 121, 147 Quinine, 84, 121, 147 R Race, 126, 147 Racemic, 126, 147 Radiation, 53, 113, 126, 128, 129, 130, 133, 134, 135, 136, 147, 148, 158 Radiation therapy, 129, 135, 136, 147, 158 Radioactive, 133, 134, 135, 136, 141, 147, 148, 158 Radiolabeled, 136, 148, 158 Radiological, 18, 143, 148 Radiology, 148 Radiotherapy, 118, 136, 148, 158 Random Allocation, 148 Randomization, 5, 7, 148 Randomized, 5, 7, 9, 10, 12, 15, 18, 21, 25, 26, 35, 39, 49, 53, 127, 148 Randomized clinical trial, 5, 12, 148 Randomized Controlled Trials, 21, 148 Ranitidine, 84, 148 Receptor, 4, 80, 81, 111, 114, 126, 137, 148, 150 Rectum, 130, 134, 148 Recurrence, 9, 24, 25, 86, 148 Red blood cells, 129, 140, 148, 151 Reductase, 137, 139, 149, 151 Refer, 1, 118, 122, 141, 149, 155 Refraction, 149, 152 Refractory, 14, 30, 40, 44, 50, 60, 61, 65, 76, 85, 87, 149 Regimen, 13, 127, 149 Registries, 8, 149 Remission, 138, 148, 149 Renin, 81, 114, 149 Reperfusion, 61, 69, 79, 149 Reperfusion Injury, 149 Research Support, 8, 149 Resection, 13, 41, 149

Respiration, 13, 119, 123, 140, 149 Respiratory failure, 37, 149 Retinoids, 84, 149 Retrospective, 9, 32, 149 Retrospective Studies, 9, 149 Retrospective study, 32, 149 Reversion, 24, 47, 119, 149 Ribose, 111, 150 Risk factor, 3, 150 Rodenticides, 143, 150 S Salicylate, 150 Salicylic, 150 Salicylic Acids, 150 Saphenous, 123, 150 Saphenous Vein, 123, 150 Saponin, 68, 150 Schizoid, 150, 158 Schizophrenia, 150, 158 Schizotypal Personality Disorder, 150, 158 Screening, 68, 121, 150 Secretion, 52, 121, 132, 139, 148, 150 Sedative, 116, 120, 150 Selective estrogen receptor modulator, 150, 154 Semisynthetic, 113, 150 Sensibility, 113, 150 Sepsis, 81, 150 Septal, 37, 150 Sequester, 150, 154 Serotonin, 115, 130, 141, 150, 156 Serous, 133, 150 Serum, 38, 42, 112, 113, 122, 150, 151 Sex Characteristics, 151 Shock, 10, 113, 120, 151, 155 Side effect, 80, 85, 89, 111, 115, 140, 151, 155, 157 Silymarin, 61, 67, 69, 139, 151 Simvastatin, 26, 151 Skeletal, 136, 147, 151, 152 Skin Pigmentation, 23, 151 Sludge, 84, 151 Small cell lung cancer, 67, 151 Small intestine, 133, 151 Smooth muscle, 118, 132, 140, 151, 152, 153 Social Environment, 147, 151 Social Security, 148, 151 Social Support, 8, 151 Sodium, 26, 38, 61, 66, 80, 84, 112, 128, 147, 151, 155

167

Sodium Channels, 61, 80, 128, 147, 151, 155 Soft tissue, 118, 152 Solid tumor, 68, 127, 152 Solvent, 77, 142, 143, 152 Sotalol, 19, 30, 32, 40, 41, 49, 60, 152 Sound wave, 122, 152 Spasm, 138, 152 Specialist, 101, 126, 152 Species, 124, 129, 138, 139, 140, 147, 152, 154, 155, 156, 157 Spectrum, 74, 124, 139, 152 Spinal cord, 115, 118, 120, 121, 123, 141, 152, 153 Spirometry, 44, 152 Squamous, 152, 157 Sterile, 82, 113, 152 Steroid, 4, 124, 151, 152 Stimulant, 126, 132, 136, 152, 154 Stimulus, 123, 129, 135, 152, 154 Stomach, 129, 131, 133, 140, 143, 151, 152 Stress, 6, 8, 116, 120, 136, 140, 142, 152, 156 Stria, 6, 152 Subacute, 135, 152 Subclinical, 69, 135, 153 Subcutaneous, 143, 153 Substance P, 129, 139, 150, 153 Substrate, 43, 128, 153 Sudden cardiac death, 7, 8, 10, 16, 49, 51, 65, 153 Sudden death, 7, 10, 11, 27, 45, 75, 79, 153 Supplementation, 67, 153 Suppository, 145, 153 Suppression, 16, 25, 37, 41, 46, 76, 77, 153 Supraventricular, 29, 44, 50, 51, 66, 75, 76, 77, 81, 153 Surfactant, 75, 77, 78, 80, 81, 153 Sympathetic Nervous System, 10, 116, 153 Sympathomimetic, 126, 129, 136, 141, 153 Symptomatic, 12, 39, 40, 41, 48, 49, 76, 77, 128, 130, 153 Synapse, 111, 145, 153, 155 Synapsis, 153 Synaptic, 6, 141, 153, 154 Synaptic Vesicles, 6, 154 Systemic, 15, 84, 90, 113, 115, 118, 119, 129, 132, 135, 136, 148, 154, 156, 157, 158 Systemic lupus erythematosus, 15, 154 Systolic, 133, 154 T Tachyarrhythmia, 39, 154 Tacrine, 84, 154

Tamoxifen, 84, 150, 154 Teratogenic, 126, 154 Thalassemia, 117, 154 Therapeutics, 26, 34, 43, 47, 50, 52, 55, 65, 75, 90, 154 Threshold, 4, 32, 34, 60, 68, 129, 133, 154 Thrush, 119, 154 Thyroid, 11, 14, 20, 22, 31, 33, 45, 47, 49, 53, 54, 60, 84, 86, 133, 154, 156 Thyroid Gland, 20, 31, 133, 154 Thyroid Hormones, 154, 156 Thyroiditis, 19, 27, 154 Thyrotoxicosis, 14, 18, 27, 28, 31, 32, 38, 39, 41, 42, 45, 48, 49, 50, 51, 52, 53, 54, 69, 154 Thyroxine, 67, 112, 154 Tocainide, 45, 155 Tolerance, 33, 111, 155 Tone, 123, 155 Tonic, 119, 123, 155 Torsades de Pointes, 42, 155 Torsion, 135, 155 Toxic, iv, 83, 121, 124, 125, 128, 134, 141, 155 Toxicokinetics, 155 Toxicology, 60, 61, 62, 66, 68, 70, 96, 155 Toxin, 6, 155 Toxoplasmosis, 116, 155 Trachea, 118, 154, 155 Transfection, 117, 155 Translation, 129, 155 Translocation, 129, 155 Transmitter, 115, 126, 138, 141, 154, 155 Transplantation, 14, 22, 28, 35, 134, 155 Trauma, 141, 155 Tremor, 138, 156 Troglitazone, 84, 156 Tryptophan, 122, 150, 156 Tuberculosis, 136, 137, 150, 156 Tuberculostatic, 136, 156 Tyrosine, 126, 156 U Urinary, 36, 121, 134, 156 Urine, 114, 134, 156 Urticaria, 113, 137, 156 V Vaccine, 146, 156 Vagina, 119, 156 Vaginitis, 119, 156 Vascular, 24, 36, 47, 84, 113, 118, 135, 144, 154, 156 Vascular Resistance, 113, 156

168

Amiodarone

Vasculitis, 19, 55, 156 Vasoconstriction, 126, 129, 156 Vasodilation, 61, 117, 156 Vasodilator, 126, 132, 141, 143, 156 Vein, 19, 113, 135, 141, 150, 156 Venous, 22, 146, 156, 157 Venous Pressure, 22, 156 Venous Thrombosis, 156, 157 Ventricle, 9, 30, 116, 123, 147, 154, 156, 157 Ventricular, 5, 9, 10, 11, 15, 16, 17, 19, 20, 23, 27, 32, 37, 39, 41, 43, 45, 46, 48, 49, 55, 56, 57, 60, 65, 68, 75, 76, 77, 80, 81, 87, 113, 123, 127, 128, 130, 146, 155, 157 Ventricular Dysfunction, 9, 10, 127, 157 Ventricular fibrillation, 19, 27, 48, 55, 56, 68, 76, 155, 157 Ventricular Function, 15, 75, 157 Venules, 118, 119, 157 Verapamil, 61, 157

Vesicular, 6, 61, 157 Veterinary Medicine, 61, 95, 157 Vinblastine, 60, 65, 157 Vinca Alkaloids, 157 Vincristine, 67, 157 Vindesine, 68, 157 Vinyl Chloride, 84, 157 Virulence, 116, 155, 157 Virus, 74, 111, 157 Vitro, 157 Vivo, 157 W Warfarin, 18, 20, 42, 50, 157 White blood cell, 114, 137, 138, 140, 157 Windpipe, 154, 157 Withdrawal, 28, 158 X X-ray, 136, 141, 147, 148, 158 X-ray therapy, 136, 158

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